key: cord-0770367-6mb7a7rq
authors: Sobh, Mahmoud M.; Abdalbary, Mohamed; Elnagar, Sherouk; Nagy, Eman; Elshabrawy, Nehal; Abdelsalam, Mostafa; Asadipooya, Kamyar; El-Husseini, Amr
title: Secondary Osteoporosis and Metabolic Bone Diseases
date: 2022-04-24
journal: J Clin Med
DOI: 10.3390/jcm11092382
sha: ce39824010e2717b592b932ef5948c64afa24792
doc_id: 770367
cord_uid: 6mb7a7rq

Fragility fracture is a worldwide problem and a main cause of disability and impaired quality of life. It is primarily caused by osteoporosis, characterized by impaired bone quantity and or quality. Proper diagnosis of osteoporosis is essential for prevention of fragility fractures. Osteoporosis can be primary in postmenopausal women because of estrogen deficiency. Secondary forms of osteoporosis are not uncommon in both men and women. Most systemic illnesses and organ dysfunction can lead to osteoporosis. The kidney plays a crucial role in maintaining physiological bone homeostasis by controlling minerals, electrolytes, acid-base, vitamin D and parathyroid function. Chronic kidney disease with its uremic milieu disturbs this balance, leading to renal osteodystrophy. Diabetes mellitus represents the most common secondary cause of osteoporosis. Thyroid and parathyroid disorders can dysregulate the osteoblast/osteoclast functions. Gastrointestinal disorders, malnutrition and malabsorption can result in mineral and vitamin D deficiencies and bone loss. Patients with chronic liver disease have a higher risk of fracture due to hepatic osteodystrophy. Proinflammatory cytokines in infectious, autoimmune, and hematological disorders can stimulate osteoclastogenesis, leading to osteoporosis. Moreover, drug-induced osteoporosis is not uncommon. In this review, we focus on causes, pathogenesis, and management of secondary osteoporosis.

Osteoporosis is a condition characterized by bone fragility, secondary to either low bone mineral density (BMD) and/or microarchitectural deterioration that increases fracture risk. Postmenopausal estrogen deficiency is the primary cause of osteoporosis. In addition to postmenopausal women with primary osteoporosis (postmenopausal or age-related), more than half of perimenopausal and postmenopausal women referred to an osteoporosis center had one or more risk factors of secondary osteoporosis [1] . A fracture risk assessment tool (FRAX) helps to estimate the 10-year fracture risk by using clinical and radiological data. These clinical data include some, but not all, secondary causes of osteoporosis, such as smoking, excessive alcohol intake, type I diabetes mellitus, hyperthyroidism, chronic liver disease, and malnutrition [2] . Various secondary causes of osteoporosis are mentioned in Figure 1 . Patients with newly diagnosed osteoporosis should be thoroughly evaluated including their history, a physical examination, and routine laboratory testing for detection of secondary causes. A systematic approach for detection of the underlying causes is illustrated in Figure 2 . The management approach of patients with secondary osteoporosis is summarized in Figure 3 . Proper recognition of the etiology of osteoporosis is an essential step in improving bone health, preventing further bone loss. Those patients can benefit from balanced nutrition, physical exercise, and avoiding long term glucocorticoid usage and other drugs that have negative impact on bone health. Using antiosteoporotic therapies in patients with high risk of fractures is recommended; the mechanism of action of the commonly used antiosteoporotic medications are illustrated in Figure 4 . This article comprehensively discusses epidemiology, the various causes and pathogenesis of secondary osteoporosis. This topic not only covers the bone quantity problem but focuses on quality as well. Furthermore, the up-to-date management of secondary osteoporosis is thoroughly discussed. Those patients can benefit from balanced nutrition, physical exercise, and avoiding long term glucocorticoid usage and other drugs that have negative impact on bone health. Using antiosteoporotic therapies in patients with high risk of fractures is recommended; the mechanism of action of the commonly used antiosteoporotic medications are illustrated in Figure 4 . This article comprehensively discusses epidemiology, the various causes and pathogenesis of secondary osteoporosis. This topic not only covers the bone quantity problem but focuses on quality as well. Furthermore, the up-to-date management of secondary osteoporosis is thoroughly discussed. Pragmatic diagnostic approach for newly diagnosed patients with osteoporosis. A systematic approach for the analysis and detection of a secondary cause of osteoporosis is recommended for all patients with a new diagnosis of osteoporosis. A full history and physical examination followed by a routine laboratory investigation for the most common and simple underlying causes of osteoporosis are required for most cases. Some additional investigation may be considered after routine lab for the suspected cases. CKD, chronic kidney disease, CRP: Approach for prevention and management of secondary osteoporosis. Correction of the underlying causes of secondary osteoporosis is the cornerstone of prevention and treatment. All patients can benefit from non-pharmacological intervention, DEXA scan and assessment of fracture risk. Anti-osteoporotic medications (antiresorptives and osteoanabolics) can be used in selected cases with high fracture risk. DEXA: dual-energy X-ray absorptiometry, FRAX: fracture-risk algorithm, SERM: Selective estrogen receptor modulators. Figure 4 . Mechanism of action of common antiosteoporotic medications. Antiosteoporotic medications can be divided into two main categories: 1. Antiresorptives "on the right side" act mainly by inhibiting osteoclasts. Bisphosphonates act by inhibiting osteoclast differentiation from osteoclast precursors. The monoclonal antibody "denausumab" inhibits osteoclast differentiation by binding to RANKL, preventing its interaction with RANK. SERMs increase OPG production, thus inhibiting osteoclastogenesis. 2. Osteoanabolics "on the left side" stimulate bone formation via activation of PTH (teriparatide) or PTH-related peptide (abaloparatide) receptors. Romosuzumab is an anti-sclerostin monoclonal antibody. Thus, it stimulates osteoblast differentiation and function. MSC: mesenchymal stem cells, HSC: hematopoietic stem cells, SERMs: selective estrogen receptor modulators, OPG: osteoprotegerin, RANK: Receptor activator of nuclear factor κ B, RANKL: receptor activator of nuclear factor kappa-B ligand. this figure was created with BioRender.com (accessed on 1 February 2022).

Chronic kidney disease (CKD) is a well-established risk factor for bone loss [3] . The incidence of bone loss and fracture risk increases with decline in kidney function. Osteoporosis was reported in up to 32% of CKD patients, while osteopenia was found in about half [3] [4] [5] [6] . However, the magnitude of the problem might be higher for various reasons. First, there is a high prevalence of vascular calcification in CKD patients, which results in a higher estimation of vertebral bone mass by DXA [7] . Second, CKD patients do not have a bone mass/quantity problem only, but a bone quality disorder as well [8] . Third, there is underutilization of osteoporosis diagnostic tools in CKD patients, despite the KDIGO recommendations. Up to 30-50% of fractured CKD patients had a T-score higher than −2.5 [9, 10] . Advanced CKD patients have up to an 8-fold higher fracture risk when compared to the general population [11] . Osteoporotic fractures lead to a deleterious effect on the quality of life in CKD patients. One-year mortality after having a hip fracture is 17-27% in the general population [12, 13] , while it is up to 64% in patients with end-stage kidney disease (ESKD) [14, 15] .

Renal osteodystrophy (ROD), medication usage, hypogonadism, systemic inflammation, acidosis, and concurrent systemic illnesses contribute to bone loss in patients with bisphosphonates in patients with advanced CKD might induce LTBD and increase the risk of atypical femur fracture [46] . Denosumab has been shown to improve BMD and reduce bone turnover in CKD patients in observational studies and small randomized control trials (RCTs) [47, 48] . As opposed to bisphosphonates, it is not excreted through the kidneys, however close monitoring of serum calcium and vitamin D should be conducted for the risk of hypocalcemia.

On the other hand, osteoanabolics (teriparatide, abaloparatide, and romosozumab) have a promising role in mitigating bone loss in patients with LTBD. Teriparatide has been used in advanced CKD patients in several studies [49] [50] [51] [52] . Abaloparatide was safe and effective in the early stages of CKD [53] . Romosozumab increased BMD in patients with mild to moderate CKD [54] and in dialysis patients [55] .

Diabetes is a chronic metabolic disease associated with an increased risk of fragility fracture. Adults with Type 1 diabetes mellitus (T1DM) have a greater risk of fracture, especially non-vertebral fracture, than those with type 2 diabetes (T2DM) [56, 57] . Nevertheless, vertebral fractures are not uncommon and associated with increased mortality, but they are often underdiagnosed because they could be asymptomatic [58] . Diabetes can compromise bone metabolism, impair cell function or damage the extracellular matrix. This results in bone loss, alteration of bone microarchitecture, reduction of bone turnover and predisposition to low trauma fracture. The pathogenesis and risk factors of brittle bone in diabetes consist of obesity, increased insulin resistance, blood sugar disturbances, production of advanced glycation end products, muscle dysfunction, macro-and microvascular complications, and medications. Moreover, the associated comorbidities, such as thyroid disorders, gonadal dysfunction, and malabsorption may contribute to bone loss [59, 60] . Notably, T1DM has been associated with reduced osteoblast activity, lower or similar BMD, and a higher risk of fracture [56, [61] [62] [63] . Whereas T2DM is associated with an increased rate of bone loss and fracture, even with normal or high BMD [56, 64] . A T-score threshold of −2.0 was suggested as a trigger for therapeutic intervention in T2DM [65] . However, the bone area at the total hip is a better surrogate for fragility fracture in elderly patients with T2DM compared to BMD [66] .

Diabetes mainly affects bone quality, including disturbed bone material properties and increased cortical porosity, which are not measurable with BMD-DXA [59, 67] . This emphasizes that bone density measurement by DXA underestimates the fracture risk in diabetic patients [68] . Trabecular bone score [69] , peripheral quantitative computed tomography (pQCT), pQCT-based finite element analysis (pQCT-FEA) [70] , and high resolution peripheral quantitative computed tomography (HR-pQCT) [71] are better tools to estimate fracture risk in diabetic patients. Invasive methods, such as microindentation and bone histomorphometry, are expensive and not widely available [68, 72] .

Diabetes causes skeletal fragility and applying strategies to reduce fracture is crucial. Furthermore, it seems there is a correlation between the degree of blood sugar control and the risk of fracture. [73, 74] . In a large cohort study, there was a cubic relationship between HbA1c and risk of fracture [75] . Thiazolidinediones should be avoided in diabetic patients with increased bone fragility [76] . Moreover, there is growing evidence suggesting a negative outcome of sodium glucose cotransporter 2 (SGLT2) inhibitors on bone health. Alendronate use for 3 years resulted in an increase in BMD in diabetic patients with osteoporosis [77]. Anti-osteoporotic medications (mainly bisphosphonates) appear to prevent bone loss similarly in the spines of diabetic and non-diabetic individuals in a recent systematic review [78] . Use of daily subcutaneous injections of abaloparatide (80 mcg) was associated with improvement in BMD in diabetic patients [79].

Hypogonadism is a risk factor for osteoporosis. The peak bone mass and BMD are higher in men; however, if both a man and a woman have similar BMD, the man would have a higher risk of fracture. The incidence of osteoporosis in men under the age of 70 is significantly lower compared to women because the bone loss in women occurs earlier and at a higher rate [80, 81] . Testosterone replacement therapy can improve BMD but results in hypogonadal older men were inconclusive. However, the volumetric BMD and bone strength significantly improved in hypogonadal older men who received testosterone treatment for one year [82,83].

Hypoparathyroidism is a low bone turnover condition. The information regarding fracture risk is inconsistent [84-86], but patients with nonsurgical hypoparathyroidism seem to have a higher risk of vertebral fracture [86] [87] [88] . This could be potentially due to a longer period of bone changes in nonsurgical hypoparathyroidism compared to surgical hypoparathyroidism [86] . Therefore, we would speculate that the higher fracture risk is due to over-maturation and impaired quality of the bone. They have higher BMD by DXA at all skeletal sites, especially at the lumbar spine [89] . Furthermore, they typically have normal [89-91] or low [92] trabecular bone scores and are classified as degraded microarchitecture. Compared to the age and sex-matched controls, they often have higher volumetric BMD (trabecular and cortical), and higher cortical area and thickness by pQCT [89,93]. Nevertheless, HR-pQCT showed increased cortical volumetric BMD, but reduced cortical thickness and cortical porosity [89, 94] . They also seem to have normal biomechanical strength determined by finite element modeling [94, 95] , but lower bone material strength index, measured by impact microindentation, than controls [86, 96] . Calcium and vitamin D supplements are widely used. However, the long-term safety and efficacy of this practice are not very well studied. Donovan Tay et al. reported that long-term use of PTH (1-84) therapy reduced supplemental calcium and vitamin D requirements and increased lumbar spine and total hip BMD [97] . PTH (1-84) reduced urinary calcium and serum phosphorus levels and improved quality of life without increasing serious adverse events, compared to traditional management [98] [99] [100] . In a recent meta-analysis, compared to PTH, active vitamin D usage was associated with similar serum calcium levels but a trend toward lower urinary calcium levels [101] . Moreover, the long-term safety is not completely recognized, and dose-dependent increased risk of osteosarcoma is reported in rat studies [102, 103] . This concern limited the long-term usage of PTH (1-84) as replacement therapy for hypoparathyroidism. Small studies reported heterogeneity regarding the efficacy of parathyroid tissue allotransplantation for treating hypoparathyroidism [104] .

Primary hyperparathyroidism (PHPT) is associated with decreased BMD and increased fracture risk across various skeletal sites, especially at the lumbar spines [105, 106] . BMD measurement by DXA is an acceptable predictor of fracture at hip and forearm but underdiagnoses vertebral fragility [107] . There are valuable tools, such as trabecular bone score, 3D-DXA [108] , bone strain index (BSI) by finite element analysis of DXA [109] , and HR-pQCT [110] , to assess bone health and predict skeletal fragility [105] . HR-pQCT revealed altered microarchitecture of cortical and trabecular bone, including reduced cortical and trabecular volumetric densities, increased cortical porosity, and heterogeneity of trabecular distributions [110, 111] . This is almost consistent with histomorphometric studies, except for preservation or even improvement of trabecular bone structure [112] . The assessment of bone material strength index at the tibia by using the impact microindentation technique showed impaired bone material properties in PHPT subjects, especially in those with fragility fracture [113] . Parathyroidectomy reduces calcium concentrations and increases BMD at different skeletal sites. It might reduce fracture risk better than active surveillance [114] , but its advantages over medical therapy regarding risk of fracture, kidney stones and quality of life lack sufficient evidence [114, 115] . Nevertheless, parathyroidectomy could improve bone strength assessed by HR-pQCT and finite element analysis [116] . In terms of medical therapy, optimization of calcium and vitamin D intake is suggested [117] . Calcium supplements can reduce PTH and increase femoral neck BMD in patients with asymptomatic PHPT [118] . There is no reason to restrict dietary calcium intake in the patients with mild PHPT, but close monitoring of calcium is necessary and calcium supplementation should be avoided in severe PHPT with elevated 1,25(OH)2D and higher serum PTH levels. Other medical therapies include bisphosphonates, cinacalcet, denosumab, and estrogen, which are appropriate for lowering calcium, increasing BMD or both [117] .

Thyroid hormones play a pivotal role in bone metabolism. Hyperthyroidism, even subclinical, is a known risk factor for osteoporosis. It is associated with increased bone turnover, decreased bone mass, and increased fracture risk [119, 120] . In addition, long-term TSH suppression in patients with differentiated thyroid cancer was associated with lower BMD in postmenopausal women [121] . Hyperthyroid women had impaired bone quality and quantity reported by HR-pQCT. Euthyroidism could improve volumetric BMD and cortical microarchitecture [119] . Overt hypothyroidism reduces bone formation. However, data on BMD and fracture risk are inconclusive [122] .

Osteoporosis happens in 30-50% [123] [124] [125] , and vertebral fractures in 30-70%, of patients with Cushing syndrome [126, 127] . Cushing syndrome leads to excess glucocorticoid production, which negatively impacts bone metabolism through suppression of growth hormone and gonadal axis, besides altering the rhythmic production of parathyroid hormone [126] . Trabecular bone loss is more pronounced in patients with Cushing syndrome. Adrenal nodules with autonomous cortisol secretion [128] , primary aldosteronism [129] , pheochromocytoma [130, 131] , and congenital adrenal hyperplasia [132] are associated with deterioration of bone quality and quantity.

Despite acromegalic patients having a higher rate of bone formation, they have an increased risk of vertebral fractures because of increased bone turnover and poor bone quality. However, they may have increased, decreased, or similar BMD, compared to the general population [133, 134] . They have higher cortical porosity and altered bone microarchitecture, which is attributed to altered bone remodeling and Wnt signaling.

Growth hormone deficiency is associated with low bone turnover osteoporosis, and loss of cortical greater than trabecular bone, which leads to increased fracture risks [135] . Growth hormone replacement initially increases bone turnover and reduces bone density. A maintenance treatment encourages improved bone mass, but its effects on fracture risk is not definite [136] . This could be due to increased DKK-1, a Wnt inhibitor, therefore increasing cortical porosity [137] .

Malabsorption and chronic liver disease are well-known causes of osteoporosis, and they are included in the FRAX. Physiologic bone metabolism requires optimum amounts of nutrients, particularly minerals and vitamins. Vitamin D is a fat-soluble vitamin, so bone loss is remarkable in diseases associated with fat malabsorption [138] [139] [140] [141] [142] [143] . Furthermore, in cases of steatorrhea, calcium absorption may be hindered by binding to excess fatty acids in the gastrointestinal (GI) lumen [144] . In this section, we will discuss the most common causes of GI-related osteoporosis.

Patients with celiac disease have a high prevalence of osteopenia and osteoporosis, 40% and 15%, respectively, even after excluding postmenopausal women [145] . It has been reported that 8% of patients with idiopathic low BMD have positive IgA anti-endomysial antibodies even though they are asymptomatic. Routine screening for celiac disease might be considered in idiopathic cases of osteoporosis [146, 147] . A gluten-free diet can significantly improve BMD [148, 149] . However, bone loss may persist due to the continuous inflammatory process leading to higher osteoclast activity and lower ability to generate bone matrix [150] .

More than 50% of patients with chronic pancreatitis, particularly smokers and alcoholics, have low BMD. Pancreatic enzymes and vitamin D replacement significantly lowered the risk of fracture [151] . Cystic fibrosis can disturb bone health through mechanisms other than malabsorption. Cystic fibrosis transmembrane conductance regulator is expressed in bone cells, thus it might have a negative impact on bone metabolism. Additionally, bone resorption increases during pulmonary exacerbations as the proinflammatory cytokines stimulate osteoclast activity [152] .

The prevalence of osteoporosis in patients with short bowel syndrome is 2-fold higher compared to matched controls [141] . Bone loss occurs because of micro and macronutrients' malabsorption. Metabolic acidosis, either caused by chronic diarrhea or D-lactic acidosis by bacterial overgrowth, can also impair bone health [153] .

Disturbed enterohepatic circulation of fat-soluble vitamins impairs bone metabolism. This is one of the main causes of bone loss in biliary disorders as primary biliary cholangitis (PBC) and sclerosing cholangitis. The prevalence of osteoporosis and fractures in PBC is up to 50% and 20%, respectively [154] [155] [156] . The etiology of chronic liver disease, alcohol, viral hepatitis, and autoimmune diseases, may contribute to the pathogenesis of hepatic osteodystrophy [154, [157] [158] [159] [160] [161] . Cirrhosis complications such as malnutrition, impaired physical activity, and hypogonadism, along with disturbed vitamin D and K metabolism [162, 163] , can aggravate bone loss.

Peptic ulcer disease is linked to osteoporosis, especially among males. Certain species of H-pylori infections may afflict bone metabolism by enhancing inflammatory status, reducing the circulatory ghrelin and estrogen levels, and increasing postprandial serotonin levels. Moreover, long-term use of PPIs can impair bone health [164, 165] .

Patients with IBD have a higher risk of bone loss [166] , poor bone quality [167, 168] , and fractures [169] [170] [171] [172] . This can be explained by malnutrition, chronic inflammatory process, and immunosuppressive drugs [171, 173, 174] . Low turnover bone disease is the predominant underlying pathology in patients with osteoporosis and IBD [175, 176] . The American College of Gastroenterology recommended using the conventional risk factors as indications for BMD screening in IBD patients using DXA scan [177] . The Cornerstone Health organization has expanded the indications for BMD screening to include maternal history of osteoporosis, malnourished or very thin patients, and amenorrheicor postmenopausal women [178] . Maldonado and colleagues highlighted the role of biomechanical CT to detect patients with an increased risk of fracture. 40% of those patients were not included in the Cornerstone checklist. Thus, IBD patients undergoing CT enterography may benefit from biomechanical CT screening for fracture risk [179] . Early suppression of the inflammatory process by anti-TNF is associated with better bone preservation [169, 180] . In addition to calcium and vitamin D optimization, bisphosphonates are relatively safe and effective treatment options [181] . In an animal study, a natural compound (emodin) has been reported to inhibit osteoclast function and prevent IBD-related osteoporosis [182] .

Patients with irritable bowel syndrome have a higher incidence of osteoporosis and fragility fractures [183] . This might be explained by chronic inflammation, overactivation of the hypothalamic-pituitary-adrenal axis, nutritional deficiency, and smoking. Further studies are needed to confirm the underlying mechanisms and to establish a treatment approach [184] .

Microbiota is considered a hidden organ that has a bidirectional interaction with cellular responses. Certain species of microbiota are linked to osteoporosis and autoimmune diseases such as IBD, PBC, and sclerosing cholangitis [185, 186] . The beneficial effects of probiotics were explained experimentally by manipulating the expression of OPG/RANKL, Wnt10b, and inflammatory cytokines [186, 187] .

Other GI disorders with increased risk of osteoporosis include post-gastrectomy [188] , atrophic gastritis [189, 190] , and bariatric surgeries [191] .

Nutritional factors can potentially affect bone mass, metabolism, matrix, and microarchitecture. Insufficient nutrition leads to deficiency of protein, vitamins, and minerals, particularly calcium, phosphorus, and magnesium, which are essential for bone health [192] . The recommended daily calcium intake for adults is between 800-1200 mg daily [32, 193] , while it is 700 mg and 320-420 mg for phosphorus and magnesium, respectively [194] . The daily protein requirement is recommended to be 0.8 gm/kg for adults and 1-1.2 gm/kg for the elderly [195, 196] . The vitamin D daily requirement ranges from 800 to 1000 IU [197] .

Malnutrition can happen either because of poor nutrient intake, increased losses, and/or increased demand [198] . Bad dietary habits, anorexia nervosa, bulimia nervosa, prolonged total parental nutrition (TPN), bariatric interventions, and excess alcohol intake can cause secondary osteoporosis [199] . As osteoporosis and fractures are associated with many life-threatening events, their prevention is essential via balanced diet and physical exercise [200] .

Starvation, the most severe form of malnutrition, can be caused by various socioeconomic, environmental, and medical factors [201] . Starvation can negatively affect bone quantity and quality through minerals, vitamins, and collagen type I deficiency [201, 202] . There is a positive relationship between malnutrition during early life, or even in utero, and early incidence of osteoporosis and fractures [203] [204] [205] [206] [207] .

Vitamin D deficiency results in decreased calcium absorption and hypocalcemia leading to secondary hyperparathyroidism, consequently stimulating bone turnover and decreased BMD [208] . Treatment with vitamin D supplements has beneficial effects on bone health in patients with 25-hydroxy vitamin D levels less than 30 nmol/L [209, 210] . On the other hand, prophylactic doses of vitamin D have a debatable role in the prevention of osteoporosis and fractures. [211] [212] [213] [214] [215] [216] .

Many observational studies reported a positive relationship between body mass index (BMI) and BMD [217] . Moreover, previous studies demonstrated that obesity could protect against fractures [218, 219] . However, more recent studies did not show a positive impact of obesity on bone [220] . The Look AHEAD trial reported a modest increase in bone loss at the hip with intensive non-surgical weight loss interventions in obese type 2 diabetics [221, 222] . Moreover, most bariatric surgeries were associated with bone loss and fragility [191, 223] . This may be explained by mechanical unloading, secondary hyperparathyroidism due to malabsorption of calcium and vitamin D, decreased estrogen, leptin, and ghrelin, and increased adiponectin levels [191, 224, 225] . Therefore, it is recom-mended to receive adequate calcium and vitamin D and to monitor BMD after bariatric surgeries [226] .

Patients with anorexia nervosa extremely limit their food intake because they are scared of weight gain [227] . This can lead to several medical complications including bone loss [228] with a 2-7-fold increased risk of fractures [229, 230] . This is not only because of nutritional deficiencies but hormonal disturbances as well [231] . On the other hand, improving nutritional status corrects the endocrinological disorders and BMD in these patients [232] . Anti-osteoporotic medications may help to ameliorate bone loss in patients with persistently low BMI and amenorrhea [233] . Residronate use, either alone or combined with transdermal testosterone, resulted in improved spinal BMD [234, 235] . Moreover, physiological doses of transdermal estrogen lead to increased spinal and hip BMD [236] . In a recent RCT, sequential therapy with recombinant human IGF-1 and risedronate was superior to risedronate alone in improving lumbar spine BMD in women with anorexia nervosa [237] . Furthermore, Fazeli et al. reported a significant increase in lumbar spine BMD after 6 months of teriparatide use [238] .

Patients with prolonged TPN have an osteoporosis prevalence of 40 to 100% [239] [240] [241] . Despite TPN improving nutritional status, the prolonged need for TPN may induce dysbiosis [242] , decreased gut calcium, and phosphorus absorption [239] . Moreover, it can induce hypercalciuria because of the hyperfiltration secondary to high amino acid infusion [243] . Routine vitamin D monitoring and management are necessary for patients with prolonged TPN because vitamin D deficiency is very prevalent among these patients [239] . Bisphosphonates improved BMD in patients with TPN-associated osteoporosis [244, 245] .

Bad dietary habits have been reported to be associated with osteoporosis. High dietary sugar may lead to osteoporosis [246] by glucose-induced hypercalciuria, hypermagnesuria [247, 248] , and decreasing vitamin D activation [249] . In addition, hyperglycemia can decrease osteoblast proliferation and increase osteoclast activation [250, 251] . On the other hand, the effect of dietary salt on bone health is unclear [252] .

Heavy alcohol intake has been associated with decreased BMD [253] . Mechanistically, it directly reduces osteoblast activity and increases osteoclastogenesis [254] [255] [256] . Indirectly, it can cause changes in body composition [257] and alterations in various hormones, including PTH, vitamin D, testosterone, and cortisol [258] . Alcohol abstinence may improve bone metabolism and increase BMD [259, 260] .

Drug-induced osteoporosis is the second most common cause of secondary osteoporosis. Despite their well-known adverse events, glucocorticoids are still one of the cornerstone immune-suppressive/modulator and anti-inflammatory therapies. Up to 40% of patients on long-term glucocorticoid therapy suffer from fractures during their lifetime [261, 262] .

Areas with high trabecular bone, such as lumbar spine and hip trochanter, are the classic sites for glucocorticoid-induced fractures [263] . Robust bone loss may reach up to 20% within the first year of therapy, and subsequently decline to 1 to 3% annually [264, 265] . The fracture risk with glucocorticoid therapy is dose and time-dependent [262] . The impact of glucocorticoids on bone has been linked to their cumulative effect, which disturbs both bone quantity and quality. Glucocorticoids can induce bone loss irrespective of the route of administration. For instance, long-term inhaled glucocorticoids were associated with a 10% loss of BMD [266, 267] . Even controlled-release budesonide and topical corticosteroid can negatively impact bone health [268, 269] .

Glucocorticoids initially decrease bone formation and increase RANKL/osteoprotegerin ratio, inducing high bone resorption [270, 271] . The mechanism of bone loss with long-term usage is more attributed to suppressed bone formation rather than increased bone resorption. This could be due to the downregulation of the Wnt signaling pathway which impairs the osteoblast activity [272] . Additionally, glucocorticoids have an indirect impact on bone through their effects on calcium homeostasis, parathyroid gland activities, and vitamin D metabolism [273, 274] . Furthermore, glucocorticoids lead to loss of muscle mass and strength which increases the risk of falls and fractures. They can also induce hypogonadism which decreases the anti-resorptive effect of testosterone and/or estrogen [275] .

The use of a DXA scan and FRAX after 6 months of glucocorticoid therapy is recommended for those with a history of fragility fracture, patients of 40 years of age or older, and those with major osteoporotic risk factors [276] .

For prevention of glucocorticoid-induced osteoporosis, daily intake of 1000-1200 mg calcium and 600-800 units of vitamin D, along with lifestyle modification, are highly recommended [275] . For adults with high risk of fracture, treatment with oral bisphosphonate is the preferred line of therapy [276] . Teriparatide is also effective in preventing and treating glucocorticoid-induced bone loss [277] .

Antidepressants like selective serotonin reuptake inhibitors and monoamine oxidase inhibitors can induce low bone density and increase incidence of fracture [278] [279] [280] [281] . It is not clear how these medications affect bone health, but it may be attributed to diminished osteoblast proliferation through the serotonin receptors and transporters [282] .

Many studies showed significant bone loss with long-term use of antiepileptic drugs [283] [284] [285] . The pathogenesis is multifactorial, however accelerated vitamin D metabolism is a crucial co-player [286] [287] [288] [289] . Bone loss occurs as a result of bone remodeling abnormalities rather than abnormal mineralization [290] [291] [292] .

Aromatase inhibitors, adjuvant long-term therapies for breast cancer, lead to abrupt deprivation of estrogen and consequently, bone loss [293] . Moreover, concomitant use of gonadotropin-releasing hormone agonists induces up to 7% annual BMD loss [294] . The use of gonadotropin-releasing hormone agonists in prostate cancer patients is associated with increased fracture risk [295] [296] [297] .

Antidiabetic medications can impact bone health either positively or negatively. Peroxisome proliferator-activated receptor gamma (PPARγ) plays an important role in the regulation of bone formation and energy metabolism, along with insulin sensitivity [298, 299] . Its stimulation by thiazolidinediones induces bone resorption and inhibits bone formation [300] . Thiazolidinediones decreased the BMD and increased the risk of osteoporosis when compared to other anti-diabetic medications [301] . The effects of sodium-glucose cotransporter-2 (SGLT2) inhibitors on bone metabolism and fracture risk are receiving more attention because of their wide use. They may increase bone turnover, disturb bone microarchitecture, and reduce BMD [302] . In a recent study, Koshizaka and colleagues reported increased TRAP 5b with no change in BMD in a 24-week RCT [303] .

In 2010, the FDA released a warning against long-term use of proton pump inhibitors (PPIs) as it may increase the incidence of osteoporosis and fracture risk [304] . The limited available evidence suggested that this might happen through histamine over-secretion [305] , and affecting mineral homeostasis [306, 307] . There is inconsistent data regarding the impact of PPIs on BMD.

Despite the negative effect of anticoagulants on bone metabolism having been studied for a long time, such effect is still debatable, and the underlying mechanisms are still poorly understood [308] . Unfractionated heparin was associated with significant bone loss compared to low molecular weight heparin [309] [310] [311] . Long-term use of warfarin was associated with decreased BMD and TBS [312] . In a recent study, this negative effect on bone was more pronounced in warfarin but was also found in direct oral anticoagulants [313] .

Chronic active infections are not infrequent causes of bone loss, mainly due to cytokine release that stimulates osteoclastogenesis and suppresses osteoblast function. Human immunodeficiency virus (HIV)-infected patients have a three times higher prevalence of osteoporosis and up to four-fold increased risk of fractures compared to the general population [314, 315] . This might be directly attributed to the HIV infection or secondary to the use of antiretroviral therapy (ART), concomitant alcohol use, smoking, associated hypogonadism, malnutrition, hepatitis B and/or C co-infection, and vitamin D insufficiency [316] [317] [318] [319] [320] . HIV infection promotes osteoblast apoptosis and osteoclast activation [321] [322] [323] [324] [325] . Furthermore, HIV infection induces a state of chronic inflammation in addition to immune system activation afflicting bone health [326] [327] [328] . Tenofovir disoproxil fumarate (TDF) is associated with osteoporosis and fractures more than the newer ART [329] [330] [331] [332] , as it induces multiple renal tubular defects and mineral losses [333, 334] . The European AIDS Clinical Society (EACS) [335] guidelines recommend tenofovir alafenamide (TAF) as a first-line therapy instead of TDF in patients with progressive osteopenia or osteoporosis, as it is less toxic to the renal tubules [336, 337] . Bisphosphonates are used effectively for the treatment of HIV-related bone disease [338] ; however, bone anabolic drugs have not been adequately studied [315] .

Hepatitis B and C viral (HBV; HCV) infections even without subsequent liver cirrhosis is associated with an increased risk of osteopenia and osteoporosis [158, [339] [340] [341] . Furthermore, previous studies reported that the risk of osteoporosis was still higher in patients with HBV and HCV infections even after adjustment for other osteoporosis risk factors [158, 342] . Of note, previous studies reported an increased risk of fractures in patients with HIV and HCV co-infection compared with HIV-infected patients [319] . Interestingly, HCV clearance led to a two-thirds reduction in fracture risk in postmenopausal women with osteoporosis [343] .

Herpes zoster infection is associated with osteoporosis [344, 345] . This negative effect on bone health may be due to the upregulation of inflammatory cytokines, especially in patients with post-herpetic neuralgia [346, 347] .

COVID-19 might predispose patients to osteoporosis [348] . This may be because of associated pro-inflammatory cytokine production and prolonged immobilization in severe cases [349] . Furthermore, there might be direct sequelae of infection on the skeleton [350] . The virus can decrease ACE2 expression in both osteoblasts and osteoclasts [351] , leading to disordered bone formation and resorption. In addition, corticosteroids used in the treatment of COVID-19 have a negative impact on bone.

Osteomyelitis is commonly associated with significant bone loss and subsequent fragility fractures [352] . This is mainly attributed to the upregulation of inflammatory cytokines such as IL-1, IL-6, and TNFα with subsequent activation of RANKL and inhibition of osteoprotegerin [353, 354] .

Patients with active TB and TB survivors with pulmonary fibrosis have increased risk of osteoporosis [342, 355] . Chronic systemic inflammation, concomitant malnutrition, and vitamin D deficiency are the main contributors to bone loss [354, [356] [357] [358] .

Hematologic disorders are potentially able to damage bone through direct cellular effects or indirectly, mediated by several circulating factors [359] . The bone loss occurs mainly due to an imbalance between RANKL/RANK and WNT signaling pathways with subsequently increased bone resorption and decreased bone formation [360] [361] [362] [363] .

Anemia can lead to bone resorption and increases bone fragility [364, 365] . Iron deficiency may negatively impact cytochromes' P450 activity, which is essential for vitamin D metabolism and bone health [366] . β thalassemia causes ineffective erythropoiesis and bone marrow expansion that leads to medullary destruction and cortical thinning [367] . Moreover, pubertal delay, cytokine disturbances, growth hormone deficiency, iron bone deposition, deferoxamine-induced bone dysplasia, and vitamin D deficiency can further contribute to inadequate bone health in thalassemia patients [368] [369] [370] [371] [372] [373] . Bisphosphonate may improve BMD [373, 374] , however its effect on fracture rate is uncertain in patients with thalassemia [375] . There is limited information but promising results observed by using denosumab or teriparatide to increase bone density in thalassemia patients [376, 377] .

The estimated prevalence of secondary osteoporosis in hemophilia patients is up to 58.7% [378] . The underlying mechanisms for low bone mass include vitamin D deficiency, limited physical activity secondary to hemophilic arthropathy, and the acquisition of osteoporosis-linked blood-born infections such as HIV [379] [380] [381] . In addition, Factor VIII deficiency is directly associated with increased bone resorption and decreased formation secondary to the imbalance in OPG/RANK/RANKL system [382, 383] . Screening for osteoporosis should be implemented in the underweight, those with fragility fractures, HIV, and/or advanced hemophilic arthropathy [384] . Replacement of the deficient factor could minimize joint bleeding and hemoarthropathy and subsequently reduce the risk and progression of osteoporosis [385] .

Both monoclonal gammopathy of undetermined significance and multiple myeloma patients are at increased hazard for osteoporosis and fragility fractures [386, 387] . Myeloma cells stimulate the release of cytokines, IL-6, and IL-7, leading to activation of the RANKL/ RANK pathway and enhanced bone resorption [361] . On the other hand, the expression of WNT inhibitors, Dkk-1, and secreted frizzled protein-2 is enhanced, leading to reduced bone formation [388, 389] . Several guidelines recommend myeloma screening in elderly patients with osteoporosis and/or fragility fractures [390, 391] . Bisphosphonate is recommended in myeloma patients as they have antineoplastic, immunomodulatory, and anticatabolic effects [392, 393] . Nevertheless, renal impairment which is frequent in those patients is still an important hindrance [394] and may obligate the use of other safer drugs such as denosumab [395] . In addition, treatment of multiple myeloma, such as bortezomib, and monoclonal antibodies targeting DKK1 or sclerostin can reduce bone loss [396] [397] [398] .

Osteoporosis is the most common skeletal pathology that occurs in 18 to 40% of systemic mastocytosis patients [399] [400] [401] . Bone involvement occurs due to bone marrow infiltration by mast cells, besides the release of circulating factors, such as histamine, prostaglandins, and interleukins (IL-1, IL-3, IL-6), which enhance osteoclast activity [402] . The manifestations consist of a wide clinical spectrum from asymptomatic condition to varying degrees of bone damage, such as osteopenia, osteoporosis, osteolytic lesions, and osteosclerosis [403] . Besides antiresorptive medications such as bisphosphonate and denosumab [404, 405] , interferon may improve bone pathology by controlling the disease activity [406] . Contrarily, safety concerns exist with the use of teriparatide as it may enhance the proliferation of malignant cells [407] .

In patients with solid tumors, bone damage usually occurs either as a side effect of anticancer treatment or secondary to osteolytic metastasis, most commonly from breast cancer [408] . Moreover, cytotoxic chemotherapy and hormone deprivation therapies have detrimental effects on both bone quantity and quality [409] [410] [411] . Bone loss in patients receiving aromatase inhibitors or androgen deprivation therapy is up to ten times that in age-matched healthy controls [412, 413] . Therefore, baseline and follow-up DXA scans are serially recommended based on the underlying diseases [414, 415] . Bisphosphonate is advised in aromatase inhibitor receivers with higher fracture risk [416] .

The immune system plays an important role in bone homeostasis. Activated T cells affect bone health through the secretion of various cytokines [417] . Some experimental studies detected that Th17 cells are responsible for stimulating bone resorption, while T reg cells are peculiarly associated with inhibition of bone resorption [418] . Moreover, CD8+ T cells might have a protective function through the secretion of various factors, such as osteoprotegerin and interferon-γ which have an anti-osteoclastogenesis effect [419] .

Inflammatory arthritis, including rheumatoid arthritis (RA), psoriatic arthritis, and spondyloarthropathy, is frequently associated with systemic skeletal complications, such as osteoporosis and fragility fractures [420] .

Osteoporosis prevalence in patients with RA is about 30% and increases up to 50% in post-menopausal women [421, 422] . Furthermore, a large meta-analysis revealed that patients with RA have a higher risk of fracture [423] .

RA-related osteoporosis is described by two main features: local and systemic bone loss [424] . Several mechanisms are involved in the pathogenesis of bone loss including sustained inflammation, glucocorticoid use, decreased physical activity and increased secretion of proinflammatory cytokines such as IL-6, IL-1, and TNF-α [422, 425] . Moreover, overexpression of RANKL promotes osteoclastogenesis [426] . There is enough evidence to support the role of autoantibodies in the pathogenesis of both local and systemic bone loss through osteoclast activation [427] [428] [429] .

Disease-modifying anti-rheumatic drugs (DMARDs) don't only control the inflammatory status but also help to avoid the long-term negative effects of corticosteroids on bone health [430] . The use of leflunomide was associated with a significant increase in lumbar spine BMD [431] . Moreover, TNF-inhibitors improved BMD and reduced the rate of fracture [432] . Other biological agents such as tocilizumab, rituximab, and abatacept significantly reduced bone resorption markers and RANKL expression [433, 434] . On the other hand, the impact of methotrexate on bone loss is controversial [435] .

Despite several studies demonstrating a significant association between psoriatic arthritis and bone loss/fragility fracture [436, 437] , others did not find such association [438] . Pro-inflammatory cytokines are involved in the mechanism of local bone loss [439] .

On the other hand, patients with ankylosing spondylitis (AS) have lower BMD, even in the early stage of the disease [440] . The prevalence of osteopenia and osteoporosis is about 54% and 16%, respectively, within 10 years of the disease onset [440] . A large database showed a higher risk of vertebral and non-vertebral fractures among patients with AS [441] . The use of non-steroidal anti-inflammatory drugs was associated with decreased fracture risk [441] . TNF-inhibitors increased lumbar spine and total hip BMD, however they did not decrease the rate of vertebral fractures [442] .

Osteoporosis and fragility fractures are well-known comorbidities in patients with SLE [443] . The incidence of fracture is up to 35% in this patient population [444] . Furthermore, asymptomatic vertebral, and non-vertebral fractures were associated with decreased quality of life and increased risk of mortality [445, 446] . Pro-inflammatory cytokines directly affect bone mass [447] . Organ damage can indirectly cause bone mass loss. The disease duration and severity, besides the long-term glucocorticoid usage, are the main determinants of bone loss [448, 449] . Lower levels of P1NP are predictive of bone loss and decrease BMD over 12 months in premenopausal SLE patients [450] .

Several studies showed that people with MS have lower BMD, higher rates of osteoporosis, and increased fracture risk compared to healthy controls [451] [452] [453] . Various risk factors contribute to bone loss in patients with MS, including disease duration and severity, vitamin D insufficiency, cumulative steroid dose, decreased ambulation, and inflammatory processes [453, 454] . The pro-inflammatory osteopontin levels increase in patients with MS and correlate with femur neck BMD [455] .

Smoking is incorporated within the FRAX score as a risk factor for osteoporosis [456] . It has direct harmful effects on osteogenesis and bone blood flow [457] . Indirectly, it afflicts serum levels of vitamin D, PTH [458, 459] , and sex hormones, particularly in females [460] . The effect of smoking cessation on BMD is unclear; however, it has been shown that it could increase BMD at femur and total hip [461] and reduce vertebral fractures [462] .

Osteocytes have certain mechano-receptors that use weightbearing-induced signals to orchestrate bone turnover. Immobility leads to osteocyte dysfunction and subsequent inhibition of bone formation via downregulation of Wnt/β-catenin pathway [463] . This can be a systemic disorder with prolonged immobilization or a local disease among patients with hemiparesis, spinal cord injuries, or neuromuscular diseases. Physical exercise and rehabilitation programs are essential in preventing and treating this type of bone loss. The use of antiosteoporotic medications such as bisphosphonates, denosumab, teriparatide, and romosozumab might be indicated in refractory cases [463] [464] [465] .

Genetics plays a crucial role in bone microarchitectural properties, skeletal strength, and the risk of osteoporosis. Rare, monogenic forms of osteoporosis start in childhood or young adulthood [466] . The most common one is osteogenesis imperfecta (OI), also known as 'brittle bone disease' [467] . Osteogenesis imperfecta is a genetic connective tissue disorder caused by defective bone formation, mainly due to impaired production and/or processing of type 1 collagen [468] . It is characterized by an abnormally high bone matrix mineralization. This is related to a larger number of crystals with the same volume of matrix [469, 470] . Cortical porosity, thin trabeculae, abnormal bone quality, and low bone density with associated increased risk of fracture are common findings in OI [471] [472] [473] . There is limited evidence that bisphosphonates increase BMD and decrease the risk of fracture in patients with OI [474] . Moreover, denosumab had poor and inconclusive results [475] . Notably, romosuzumab increased BMD and improved turnover biomarkers in those patients [419] . Apart from OI, whole-genome sequencing studies were able to unmask new genetic variants that are associated with osteoporosis. The expression of these genetic variants is involved in different bone-protecting functions, such as vitamin D metabolism, mesenchymal stem cell osteogenic differentiation, and bone morphogenetic proteins. Some of these variants are population-specific and others are shared between patients with low BMD from different races [476, 477] .

Osteoporotic fractures are increasing exponentially [478] and are considered one of the major health care problems [479] . Osteoporosis is associated with a negative effect on fracture healing, especially in unstable and comminuted fractures, which indicate internal fixation [480, 481] . The power of screw holding is decreased in the osteoporotic bone which, in turn, causes implant loosening, loss of fixation, and impaired healing. Antiosteoporotic medication should be considered to improve bone formation and the success rate of bone implants in osteoporotic fractures [482] .

The current review is limited by the quantity and quality of the clinical studies in this field. Few RCTs demonstrated the impact of different anti-osteoporotic medications on bone.

Secondary osteoporosis is diagnosed when bone fragility is caused by a disease, drug, or nutritional deficiencies. It is an evolving, devastating health problem. Proper diagnosis and prevention are the cornerstones of preventing further bone loss and fragility fractures. Although causal treatment is essential, antiosteoporotic medications can further decrease the risk of fractures, as well as improve fracture healing. More RCTs are required to explore the safety and efficacy of antiosteoporotic drugs in various clinical settings. 

Yield of Laboratory Testing to Identify Secondary Contributors to Osteoporosis in Otherwise Healthy Women

Interpretation and use of FRAX in clinical practice

Prevalence of osteoporosis in patients with chronic kidney disease (stages 3-5) in comparison with age-and sex-matched controls: A study from Kashmir Valley Tertiary Care Center

Bone mineral density in patients with predialysis chronic kidney disease

Bone mineral density and biochemical markers of bone metabolism in predialysis patients with chronic kidney disease

Sánchez-Polo, V. Pos-275 osteoporosis in ckd: Prevalence and associated factors in a guatemalan center

Bone Quality in CKD Patients: Current Concepts and Future Directions-Part I

Differences in bone quality in low-and high-turnover renal osteodystrophy

Treatment of Low Bone Density or Osteoporosis to Prevent Fractures in Men and Women: A Clinical Practice Guideline Update From the American College of Physicians

American association of clinical endocrinologists/american college of endocrinology clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis-2020 update executive summary

Incidence and risk factors for hip or other bone fractures among hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study

One-Year Mortality After Hip Fracture: Development and Validation of a Prognostic Index

One-year mortality after hip fracture surgery and prognostic factors: A prospective cohort study

Increased incidence of hip fractures in dialysis patients with low serum parathyroid hormone

Increased risk of mortality associated with hip fracture in the dialysis population

Definition, evaluation, and classification of renal osteodystrophy: A position statement from Kidney Disease: Improving Global Outcomes (KDIGO)

Initial FGF23-mediated signaling occurs in the distal convoluted tubule

25-Dihydroxyvitamin D3 upregulates FGF23 gene expression in bone: The final link in a renal-gastrointestinal-skeletal axis that controls phosphate transport

Severely reduced production of klotho in human chronic renal failure kidney

FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis

Fibroblast growth factor 23 impairs phosphorus and vitamin D metabolism in vivo and suppresses 25-hydroxyvitamin D-1α-hydroxylase expression in vitro

Secondary hyperparathyroidism and chronic kidney disease

Direct effect of phosphorus on PTH secretion from whole rat parathyroid glands in vitro

Parathyroid hyperplasia in uremic rats precedes down-regulation of the calcium receptor

Decreased 1, 25-dihydroxyvitamin D3 receptor density is associated with a more severe form of parathyroid hyperplasia in chronic uremic patients

Serum dickkopf-related protein 1 and sclerostin may predict the progression of chronic kidney disease in Japanese patients

Sclerostin and DKK1 circulating levels associate with low bone turnover in patients with chronic kidney disease Stages 3 and 4

Role of receptor activator of nuclear factor-κB ligand and osteoprotegerin in bone cell biology

Bone Health in Chronic Kidney Disease-Mineral and Bone Disease

Risk factors for reduced bone density in haemodialysis patients

Poor Vitamin K Status Is Associated with Low Bone Mineral Density and Increased Fracture Risk in End-Stage Renal Disease

European guidance for the diagnosis and management of osteoporosis in postmenopausal women

Bone mass and microarchitecture in CKD patients with fracture

A combination of low doses of 17 beta-estradiol and norethisterone acetate prevents bone loss and normalizes bone turnover in postmenopausal women

Diagnostic Accuracy of Noninvasive Bone Turnover Markers in Renal Osteodystrophy

Diagnostic Accuracy of Bone Turnover Markers and Bone Histology in Patients with CKD Treated by Dialysis

Discriminants of prevalent fractures in chronic kidney disease

Diagnostic usefulness of bone mineral density and biochemical markers of bone turnover in predicting fracture in CKD stage 5D patients-a single-center cohort study

Atlas of Mineralized Bone Histology

Renal osteodystrophy: What's in a name? Presentation of a clinically useful new model to interpret bone histologic findings

Changing bone patterns with progression of chronic kidney disease

Bone Quality in Chronic Kidney Disease Patients: Current Concepts and Future Directions-Part II

Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD)

Efficacy and safety of once-monthly risedronate in osteoporosis subjects with mild-to-moderate chronic kidney disease: A post hoc subgroup analysis of a phase III trial in Japan

Safety of Oral Bisphosphonates in Moderate-to-Severe Chronic Kidney Disease: A Binational Cohort Analysis

Atypical Femoral Fractures-Ongoing and History of Bone-Specific Therapy, Concomitant Diseases, Medications, and Survival

Denosumab in chronic kidney disease: A narrative review of treatment efficacy and safety

Effects of Denosumab and Alendronate on Bone Health and Vascular Function in Hemodialysis Patients: A Randomized, Controlled Trial

Treatment of Hemodialysis-Associated Adynamic Bone Disease with Teriparatide (PTH1-34): A Pilot Study

Impact of long-term cinacalcet, ibandronate or teriparatide therapy on bone mineral density of hemodialysis patients: A pilot study

Once-weekly teriparatide in hemodialysis patients with hypoparathyroidism and low bone mass: A prospective study

Impact of Weekly Teriparatide on the Bone and Mineral Metabolism in Hemodialysis Patients With Relatively Low Serum Parathyroid Hormone: A Pilot Study

Abaloparatide in patients with mild or moderate renal impairment: Results from the ACTIVE phase 3 trial

OP0297|Efficacy and safety of romosozumab among postmenopausal women with osteoporosis and mild-to-moderate chronic kidney disease

Efficacy of romosozumab in patients with osteoporosis on maintenance hemodialysis in Japan; An observational study

The risk of hip and non-vertebral fractures in type 1 and type 2 diabetes: A systematic review and meta-analysis update

Comparison of fracture risk between type 1 and type 2 diabetes: A comprehensive real-world data

Vertebral Fractures in Individuals with Type 2 Diabetes: More Than Skeletal Complications Alone

Type 2 diabetes and the skeleton: New insights into sweet bones

Receptor for AGEs, Diabetes, and Bone: Review of the Literature

Incidence of fractures in patients with type 1 diabetes mellitus-a retrospective study with 4420 patients

Bone Mineral Density across the Lifespan in Patients with Type 1 Diabetes

Bone mineral density at femoral neck and lumbar spine in adults with type 1 diabetes: A meta-analysis and review of the literature

Association between bone mineral density and type 2 diabetes mellitus: A meta-analysis of observational studies

Diagnosis and management of bone fragility in diabetes: An emerging challenge

Type 2 diabetes and Change in Total Hip Bone Area and Bone Mineral Density in Elderly Swedish Men and Women

Update on the pathogenesis and treatment of skeletal fragility in type 2 diabetes mellitus

Fracture risk in type 1 diabetes: Think beyond bone mineral density

TBS (trabecular bone score) and diabetes-related fracture risk

Bone Measures by Dual-Energy X-ray Absorptiometry and Peripheral Quantitative Computed Tomography in Young Women with Type 1 Diabetes Mellitus

Noninvasive Assessment of Skeletal Microstructure and Estimated Bone Strength in Hypoparathyroidism

Assessment of trabecular and cortical architecture and mechanical competence of bone by high-resolution peripheral computed tomography: Comparison with transiliac bone biopsy

PTH and bone material strength in hypoparathyroidism as measured by impact microindentation

Therapy of Hypoparathyroidism with rhPTH(1-84): A Prospective, 8-Year Investigation of Efficacy and Safety

Efficacy and safety of recombinant human parathyroid hormone (1-84) in hypoparathyroidism (REPLACE): A double-blind, placebo-controlled, randomised, phase 3 study

The effect of PTH(1-84) on quality of life in hypoparathyroidism

American Thyroid Association Statement on Postoperative Hypoparathyroidism: Diagnosis, Prevention, and Management in Adults

Parathyroid Hormone Replacement versus Oral Calcium and Active Vitamin D Supplementation in Hypoparathyroidism: A Meta-analysis

Defining a noncarcinogenic dose of recombinant human parathyroid hormone 1-84 in a 2-year study in Fischer 344 rats

Safety of osteoanabolic therapy: A decade of experience

Parathyroid allotransplantation to treat post-thyroidectomy hypoparathyroidism: A review of case studies

Risk of fractures in primary hyperparathyroidism: A systematic review and meta-analysis

The Risk of Fractures in Primary Hyperparathyroidism: A Meta-Analysis

Prevalence and Risk of Vertebral Fractures in Primary Hyperparathyroidism: A Nested Case-Control Study

Bone Analysis by the Trabecular Bone Score and 3D-DXA in Postmenopausal Women with Primary Hyperparathyroidism

DXA-Based Bone Strain Index: A New Tool to Evaluate Bone Quality in Primary Hyperparathyroidism

Primary hyperparathyroidism is associated with abnormal cortical and trabecular microstructure and reduced bone stiffness in postmenopausal women

Effects on bone geometry, density, and microarchitecture in the distal radius but not the tibia in women with primary hyperparathyroidism: A case-control study using HR-pQCT

Primary hyperparathyroidism: Lessons from bone histomorphometry

Bone Material Strength Index as Measured by Impact Microindentation is Low in Patients with Primary Hyperparathyroidism

Long-Term Skeletal Outcomes of Primary Hyperparathyroidism Patients After Treatment with Parathyroidectomy: A Systematic Review and Meta-Analysis

Efficacy of parathyroidectomy compared with active surveillance in patients with mild asymptomatic primary hyperparathyroidism: A systematic review and meta-analysis of randomized-controlled studies

Skeletal Microstructure and Estimated Bone Strength Improve Following Parathyroidectomy in Primary Hyperparathyroidism

Medical management of primary hyperparathyroidism: Proceedings of the fourth International Workshop on the Management of Asymptomatic Primary Hyperparathyroidism

The effects of calcium supplementation to patients with primary hyperparathyroidism and a low calcium intake

Consequences of Hyperthyroidism and Its Treatment for Bone Microarchitecture Assessed by High-Resolution Peripheral Quantitative Computed Tomography

Association of subclinical thyroid dysfunction with bone mineral density and fracture: A meta-analysis of prospective cohort studies

Effect of TSH Suppression Therapy on Bone Mineral Density in Differentiated Thyroid Cancer: A Systematic Review and Meta-analysis

Thyroid Hormone Diseases and Osteoporosis

Osteoporosis is more prevalent in adrenal than in pituitary Cushing's syndrome

Gender-related differences in the presentation and course of Cushing's disease

Bone density and microarchitecture in endogenous hypercortisolism

Consensus on diagnosis and management of Cushing's disease: A guideline update

Bone demineralization and vertebral fractures in endogenous cortisol excess: Role of disease etiology and gonadal status

Bone Evaluation by High-Resolution Peripheral Quantitative Computed Tomography in Patients With Adrenal Incidentaloma

Lower Trabecular Bone Score in Patients With Primary Aldosteronism: Human Skeletal Deterioration by Aldosterone Excess

Lower Bone Mass and Higher Bone Resorption in Pheochromocytoma: Importance of Sympathetic Activity on Human Bone

Role of deteriorated bone quality in the development of osteoporosis in pheochromocytoma and paraganglioma

Increased Prevalence of Fractures in Congenital Adrenal Hyperplasia: A Swedish Population-Based National Cohort Study

Bone turnover, bone mineral density, and fracture risk in acromegaly: A meta-analysis

Impaired Bone Microarchitecture in Premenopausal Women With Acromegaly: The Possible Role of Wnt Signaling

Growth hormone, insulin-like growth factors, and the skeleton

Should patients with adult GH deficiency receive GH replacement?

Increased serum and bone matrix levels of the secreted Wnt antagonist DKK-1 in patients with growth hormone deficiency in response to growth hormone treatment

Celiac Disease and Bone Health in Children and Adolescents: A Systematic Review and Meta-Analysis

High prevalence of osteoporosis in patients with chronic pancreatitis: A systematic review and meta-analysis

Association between primary biliary cholangitis and osteoporosis: Meta-analysis

Osteoporosis in patients with intestinal insufficiency and intestinal failure: Prevalence and clinical risk factors

Transporters for the intestinal absorption of cholesterol, vitamin E, and vitamin K

Factors influencing the absorption of vitamin D in GIT: An overview

Fat malabsorption induced by gastrointestinal lipase inhibitor leads to an increase in urinary oxalate excretion

Prevalence of osteoporosis and osteopenia in men and premenopausal women with celiac disease: A systematic review

Osteopenia in patients with clinically silent coeliac disease warrants screening

Prevalence of IgA-antiendomysial antibody in a patient cohort with idiopathic low bone mineral density

Body mass index in celiac disease and effect of a gluten-free diet on body mass index

Bone recovery after a gluten-free diet: A 5-year follow-up study

Alterations of Inflammatory and Matrix Production Indices in Celiac Disease With Low Bone Mass on Long-term Gluten-free Diet

Low Bone Mineral Density and Risk for Osteoporotic Fractures in Patients with Chronic Pancreatitis

Impact of cystic fibrosis on bone health

Bones, and Stones: Managing Complications of Short Bowel Syndrome

Osteoporosis in chronic liver disease

Osteoporosis in patients with primary biliary cirrhosis

Severity of cholestasis and advanced histological stage but not menopausal status are the major risk factors for osteoporosis in primary biliary cirrhosis

Bone changes in alcoholic cirrhosis of the liver. A histomorphometric study

Association Between Chronic Hepatitis B Virus Infection and Risk of Osteoporosis: A Nationwide Population-Based Study

Relation Between Hepatitis C Virus Exposure and Risk of Osteoporosis: A Nationwide Population-Based Study

A System to Determine Risk of Osteoporosis in Patients With Autoimmune Hepatitis

Association between iron overload and osteoporosis in patients with hereditary hemochromatosis

Hepatic Osteodystrophy-Molecular Mechanisms Proposed to Favor Its Development

Hepatic Osteodystrophy: A Global (Re)View of the Problem

Is there an association between peptic ulcer disease and osteoporosis: A systematic review and cumulative analysis

Infection by CagA-Positive Helicobacter pylori Strains and Bone Fragility: A Prospective Cohort Study

Metabolic bone disease in patients diagnosed with inflammatory bowel disease from Spain

Assessment of bone quality with trabecular bone score in patients with inflammatory bowel disease

Fractal-Based Analysis of Bone Microstructure in Crohn's Disease: A Pilot Study

Does the Antitumor Necrosis Factor-alpha Therapy Decrease the Vertebral Fractures Occurrence in Inflammatory Bowel Disease?

The incidence of fracture among patients with inflammatory bowel disease. A population-based cohort study

Risk of Fractures in Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis

Inflammatory Bowel Disease and Risk of Osteoporotic Fractures: A Meta-Analysis. Cureus

Bone loss in patients with inflammatory bowel disease: Cause, detection and treatment

Azathioprine Has a Deleterious Effect on the Bone Health of Mice with DSS-Induced Inflammatory Bowel Disease

Increased bone matrix mineralization in treatment-naive children with inflammatory bowel disease

Histomorphometric analysis reveals reduced bone mass and bone formation in patients with quiescent Crohn's disease

ACG Clinical Guideline: Preventive Care in Inflammatory Bowel Disease

Findings of CT-Derived Bone Strength Assessment in Inflammatory Bowel Disease Patients Undergoing CT Enterography in Clinical Practice

Early Initiation of Anti-TNF is Associated with Favourable Long-term Outcome in Crohn's Disease: 10-Year-Follow-up Data from the Swiss IBD Cohort Study

Efficacy and safety of bisphosphonates in management of low bone density in inflammatory bowel disease: A meta-analysis

Effects of emodin on inflammatory bowel disease-related osteoporosis

Association between Irritable Bowel Syndrome and Risk of Osteoporosis in Korean Premenopausal Women

The association between irritable bowel syndrome and osteoporosis: A systematic review and meta-analysis

Novel microbiota-related gene set enrichment analysis identified osteoporosis associated gut microbiota from autoimmune diseases

The microbiota-gut-bone axis and bone health

Effect of Bacillus subtilis C-3102 on bone mineral density in healthy postmenopausal Japanese women: A randomized, placebo-controlled, double-blind clinical trial

Risk of osteoporosis after gastrectomy in long-term gastric cancer survivors

Atrophic gastritis: A related factor for osteoporosis in elderly women

Impaired skeletal health in patients with chronic atrophic gastritis

Bariatric Surgery and Osteoporosis

Nutrition and osteoporosis prevention and treatment

The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: What clinicians need to know

US) Standing Committee on the Scientific Evaluation of Dietary Reference IntakesIntakes. Dietary reference intakes. In Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride

Evidencebased recommendations for optimal dietary protein intake in older people: A position paper from the PROT-AGE Study Group

The role of dietary protein and vitamin D in maintaining musculoskeletal health in postmenopausal women: A consensus statement from the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO)

Vitamin D supplementation: Upper limit for safety revisited?

Malnutrition: Causes and consequences

Understanding and managing secondary osteoporosis

Nutritional intake and bone health

Evidence for the adverse effect of starvation on bone quality: A review of the literature

Adaptive reduction in basal metabolic rate in response to food deprivation in humans: A role for feedback signals from fat stores

Exposure to famine in early life and the risk of osteoporosis in adulthood: A prospective study

Clinical manifestations of "Hunger Disease" among children in the ghettos during the Holocaust

Hunger whilst "in utero" programming adult osteoporosis. Rambam Maimonides Med

Higher prevalence of osteoporosis among female Holocaust survivors

Experience of famine and bone health in post-menopausal women

Vitamin D deficiency and secondary hyperparathyroidism in the elderly: Consequences for bone loss and fractures and therapeutic implications

25-hydroxyvitamin D threshold for the effects of vitamin D supplements on bone density: Secondary analysis of a randomized controlled trial

Effect of monthly high-dose vitamin D on bone density in community-dwelling older adults substudy of a randomized controlled trial

Effects of vitamin D supplementation on musculoskeletal health: A systematic review, meta-analysis, and trial sequential analysis

Effects of vitamin D supplements on bone mineral density: A systematic review and metaanalysis

Association between calcium or vitamin D supplementation and fracture incidence in community-dwelling older adults: A systematic review and meta-analysis

Effect of high-dose vitamin D supplementation on volumetric bone density and bone strength: A randomized clinical trial

Effects of combined calcium and vitamin D supplementation on osteoporosis in postmenopausal women: A systematic review and meta-analysis of randomized controlled trials

Calcium plus vitamin D supplementation and risk of fractures: An updated meta-analysis from the National Osteoporosis Foundation

Obesity and fractures in postmenopausal women

Decline in bone mass during weight loss: A cause for concern?

Weight loss-induced reduction of bone mineral density in older adults with obesity

Obesity is not protective against fracture in postmenopausal women: GLOW

Effect of 1 year of an intentional weight loss intervention on bone mineral density in type 2 diabetes: Results from the Look AHEAD randomized trial

The Look AHEAD Trial: Bone loss at 4-year follow-up in type 2 diabetes

Bariatric surgery and bone metabolism: A systematic review

Changes in bone mineral density, body composition and adiponectin levels in morbidly obese patients after bariatric surgery

Secondary hyperparathyroidism and osteopenia in women following gastric exclusion surgery for obesity

Bone health after bariatric surgery

American Psychiatric Association, A. Diagnostic and Statistical Manual of Mental Disorders

Medical complications of anorexia nervosa and bulimia

Fractures in patients with anorexia nervosa, bulimia nervosa, and other eating disorders-A nationwide register study

The clinical course of osteoporosis in anorexia nervosa: A longitudinal study of cortical bone mass

Anorexia nervosa and osteoporosis: Pathophysiology and treatment

Bone markers in osteoporosis

Pharmacological treatment options for low bone mineral density and secondary osteoporosis in anorexia nervosa: A systematic review of the literature

Effects of risedronate and low-dose transdermal testosterone on bone mineral density in women with anorexia nervosa: A randomized, placebo-controlled study

Effects of risedronate on bone density in anorexia nervosa

Physiologic estrogen replacement increases bone density in adolescent girls with anorexia nervosa

Sequential Therapy with Recombinant Human IGF-1 Followed by Risedronate Increases Spine Bone Mineral Density in Women With Anorexia Nervosa: A Randomized, Placebo-Controlled Trial

Teriparatide increases bone formation and bone mineral density in adult women with anorexia nervosa

The prevalence of vitamin D insufficiency and deficiency and their relationship with bone mineral density and fracture risk in adults receiving long-term home parenteral nutrition

Metabolic bone disease in adults receiving long-term parenteral nutrition: Longitudinal study with regional densitometry and bone biopsy

Increase in lumbar spine bone mineral content in patients on long-term parenteral nutrition without vitamin D supplementation

Changes to the intestinal microbiome with parenteral nutrition: Review of a murine model and potential clinical implications

Amino acid-induced hypercalciuria in patients on total parenteral nutrition

Intravenous pamidronate improves bone mineral density in home parenteral nutrition patients

Effect of cyclical intravenous clodronate therapy on bone mineral density and markers of bone turnover in patients receiving home parenteral nutrition

Carbonated beverages, dietary calcium, the dietary calcium/phosphorus ratio, and bone fractures in girls and boys

Influence of various nutrients and hormones on urinary divalent cation excretion

Evidence that glucose ingestion inhibits net renal tubular reabsorption of calcium and magnesium in man

Excessive fructose intake causes 1, 25-(OH) 2D3-dependent inhibition of intestinal and renal calcium transport in growing rats

Cell-mediated extracellular acidification and bone resorption: Evidence for a low pH in resorbing lacunae and localization of a 100-kD lysosomal membrane protein at the osteoclast ruffled border

Osteoporosis: A still increasing prevalence

Not salt but sugar as aetiological in osteoporosis: A review

Effect of alcohol intake on bone mineral density in elderly women: The EPIDOS study

Alcohol and bone: Review of dose effects and mechanisms

Low bone accrual is associated with osteocyte apoptosis in alcohol-induced osteopenia

Cortical bone is more sensitive to alcohol dose effects than trabecular bone in the rat

Relationships between fat and bone

Alcohol: A simple nutrient with complex actions on bone in the adult skeleton

Increased Bone Mineral Density after Abstinence in Male Patients with Alcohol Dependence

Osteoprotegerin Levels Decrease in Abstinent Alcohol-Dependent Patients

Prevalence of oral glucocorticoid usage in the United States: A general population perspective

Use of oral corticosteroids and risk of fractures

Bone density threshold and other predictors of vertebral fracture in patients receiving oral glucocorticoid therapy

Ten year probabilities of osteoporotic fractures according to BMD and diagnostic thresholds

Fracture risk with intermittent high-dose oral glucocorticoid therapy

The Skeletal Effects of Inhaled Glucocorticoids

Effects of inhaled glucocorticoids on bone density in premenopausal women

Bone mineral density in relation to efficacy and side effects of budesonide and prednisolone in Crohn's disease

Association of Potent and Very Potent Topical Corticosteroids and the Risk of Osteoporosis and Major Osteoporotic Fractures

Dexamethasone promotes osteoclastogenesis by inhibiting osteoprotegerin through multiple levels

Differential effect of glucocorticoids on calcium absorption and bone mass

Effects of low-dose prednisone on bone metabolism

Clinical review: Do glucocorticosteroids alter vitamin D status? A systematic review with meta-analyses of observational studies

Glucocorticoid-induced osteoporosis and osteonecrosis

American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis

Evaluation of the effect of selective serotonin reuptake inhibitors on bone mineral density: An observational cross-sectional study

Effects of teriparatide versus alendronate for treating glucocorticoid-induced osteoporosis: Thirty-six-month results of a randomized, double-blind, controlled trial

Use of Selective Serotonin Reuptake Inhibitors and Risk of Hip Fracture in the Elderly: A Case-Control Study in Taiwan

Association of Mental Disorders and Related Medication Use With Risk for Major Osteoporotic Fractures

Use of serotonin reuptake inhibitors and risk of subsequent bone loss in a nationwide population-based cohort study

Serotoninreuptake inhibitors act centrally to cause bone loss in mice by counteracting a local anti-resorptive effect

Osteopathies in antiepileptic long-term therapy (preliminary report)

Bone disease during chronic antiepileptic drug therapy: General versus specific risk factors

Bone mineral density in an outpatient population receiving enzyme-inducing antiepileptic drugs

Increased bone turnover in epileptic patients treated with carbamazepine

Increased bone turnover in prepubertal, pubertal, and postpubertal patients receiving carbamazepine

Possible involvement of pregnane X receptor-enhanced CYP24 expression in drug-induced osteomalacia

Bone health in young women with epilepsy after one year of antiepileptic drug monotherapy

Disturbance of calcium metabolism by anticonvulsant drugs

Dynamic differences in trabecular bone remodeling between patients after jejuno-ileal bypass for obesity and epileptic patients receiving anticonvulsant therapy

Decreased serum ionized calcium and normal vitamin D metabolite levels with anticonvulsant drug treatment

Effect of anastrozole on bone mineral density: 5-year results from the 'Arimidex', Tamoxifen, Alone or in Combination (ATAC) trial

Effect of letrozole versus placebo on bone mineral density in women with primary breast cancer completing 5 or more years of adjuvant tamoxifen: A companion study to NCIC CTG MA.17

Immediate versus deferred treatment for advanced prostatic cancer: Initial results of the Medical Research Council trial. The Medical Research Council Prostate Cancer Working Party Investigators Group

Gonadotropin-releasing hormone agonists and fracture risk: A claims-based cohort study of men with nonmetastatic prostate cancer

Canadian Urological Association guideline on androgen deprivation therapy: Adverse events and management strategies

The alliance of mesenchymal stem cells, bone, and diabetes

Effect of Insulin Resistance on BMD and Fracture Risk in Older Adults

Diabetes Working, G. Mechanisms of diabetes mellitus-induced bone fragility

Thiazolidinedione treatment decreases bone mineral density in type 2 diabetic men. Diabetes Care

Effect of dipeptidyl peptidase IV inhibitors, thiazolidinedione, and sulfonylurea on osteoporosis in patients with type 2 diabetes: Population-based cohort study

Evaluation of Bone Mineral Density and Bone Biomarkers in Patients with Type 2 Diabetes Treated With Canagliflozin

Effects of ipragliflozin versus metformin in combination with sitagliptin on bone and muscle in Japanese patients with type 2 diabetes mellitus: Subanalysis of a prospective, randomized, controlled study (PRIME-V study)

safety-information-patients-and-providers/fda-drug-safety-communication-possible-increased-risk-fractures-hip-wristand-spine-use-proton-pump#TableofEpidemiologicalStudiesevaluatingfractureriskwithprotonpumpinhibitors

Direct effects of proton pump inhibitors on histamine release from rat enterochromaffin-like cells

The effects of oral rabeprazole on endocrine and gastric secretory function in healthy volunteers

Omeprazole therapy causes malabsorption of cyanocobalamin (vitamin B12)

Anticoagulants and Osteoporosis

THU0500|Effects of long-term use of unfractionated heparin (UFH) or low-molecularweight heparin (LMWH) on bone mineral density (BMD) in patients with nephrotic syndrome

Effect of long-term use of unfractionated or low-molecular-weight heparin on bone mineral density in maintenance hemodialysis patients

Association between oral anticoagulants and osteoporosis: Real-world data mining using a multi-methodological approach

Trabecular bone score (TBS) and bone mineral density in patients with long-term therapy with warfarin

Bone density and quality in patients treated with direct-acting oral anticoagulants versus warfarin

Antiretroviral therapy and the prevalence of osteopenia and osteoporosis: A meta-analytic review

Management of osteoporosis in patients living with HIV-A systematic review and meta-analysis

Bone disease in HIV infection: A practical review and recommendations for HIV care providers

Low baseline CD4+ count is associated with greater bone mineral density loss after antiretroviral therapy initiation

Premature decline of serum total testosterone in HIV-infected men in the HAART-era

Hepatitis C co-infection and severity of liver disease as risk factors for osteoporotic fractures among HIV-infected patients

Vitamin D deficiency and altered bone mineral metabolism in HIV-infected individuals

HIV-1 triggers apoptosis in primary osteoblasts and HOBIT cells through TNFα activation

HIV-1 protein induced modulation of primary human osteoblast differentiation and function via a Wnt/β-catenin-dependent mechanism

HIV envelope gp120-mediated regulation of osteoclastogenesis via receptor activator of nuclear factor κB ligand (RANKL) secretion and its modulation by certain HIV protease inhibitors through interferon-γ/RANKL cross-talk

HIV proteins regulate bone marker secretion and transcription factor activity in cultured human osteoblasts with consequent potential implications for osteoblast function and development

HIV-1 replicates in human osteoclasts and enhances their differentiation in vitro

Is Bone Loss Linked to Chronic Inflammation in Antiretroviral-Naïve HIV-Infected Adults? A 48 Week Matched Cohort Study

Bone metabolism dysfunction mediated by the increase of proinflammatory cytokines in chronic HIV infection

Effect of antiretroviral therapy on bone turnover and bone mineral density in men with primary HIV-1 infection

Comparison of changes in bone density and turnover with abacavir-lamivudine versus tenofovir-emtricitabine in HIV-infected adults: 48-week results from the ASSERT study

Switch from tenofovir disoproxil fumarate combination to dolutegravir with rilpivirine improves parameters of bone health

Improvement in bone mineral density after switching from tenofovir to abacavir in HIV-1-infected patients with low bone mineral density: Two-centre randomized pilot study (OsteoTDF study)

Bone mineral density in virologically suppressed people aged 60 years or older with HIV-1 switching from a regimen containing tenofovir disoproxil fumarate to an elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide single-tablet regimen: A multicentre, open-label, phase 3b, randomised trial

Hypophosphatemic osteomalacia induced by tenofovir in HIV-infected patients

Osteopenia in HIV-infected men: Association with asymptomatic lactic acidemia and lower weight pre-antiretroviral therapy

The efficacy and safety of tenofovir alafenamide versus tenofovir disoproxil fumarate in antiretroviral regimens for HIV-1 therapy: Meta-analysis

Tenofovir alafenamide versus tenofovir disoproxil fumarate: Is there a true difference in efficacy and safety?

Recommendations for evaluation and management of bone disease in HIV

Bone mineral density, bone turnover, and systemic inflammation in non-cirrhotics with chronic hepatitis C

Bone mineral density measurements, bone markers and serum vitamin D concentrations in men with chronic non-cirrhotic untreated hepatitis C

Reduced bone mineral density and altered bone turnover markers in patients with non-cirrhotic chronic hepatitis B or C infection

Association between hepatitis C virus infection and osteoporotic fracture risk among postmenopausal women: A cross-sectional investigation in Taiwan

Virus clearance reduces bone fracture in postmenopausal women with osteoporosis and chronic liver disease caused by hepatitis C virus

Herpes zoster as a risk factor for osteoporosis: A 15-year nationwide population-based study

Association between Herpes Zoster and Osteoporosis: A Nested Case-Control Study Using a National Sample Cohort

Herpes zoster and the risks of osteoporosis and fracture: A nationwide cohort study

Correlation of serum inflammatory cytokine and immunoglobulin content with post-herpetic neuralgia in patients with acute herpes zoster

Diagnosis and Management of Osteoporosis during COVID-19: Systematic Review and Practical Guidance

Clinical features of patients infected with 2019 novel coronavirus in Wuhan

Managing fragility fractures during the COVID-19 pandemic

The angiotensin converting enzyme 2/angiotensin-(1-7)/Mas Receptor axis as a key player in alveolar bone remodeling

Increased fragility fracture rates in older men with osteomyelitis

Osteoimmunology at the nexus of arthritis, osteoporosis, cancer, and infection

Staphylococcus aureus protein A binds to osteoblasts and triggers signals that weaken bone in osteomyelitis

Risk of sarcopenia and osteoporosis in male tuberculosis survivors: Korea National Health and Nutrition Examination Survey

Low serum vitamin D levels and tuberculosis: A systematic review and meta-analysis

Inflammation in tuberculosis: Interactions, imbalances and interventions

Pattern and diversity of cytokine production differentiates between Mycobacterium tuberculosis infection and disease

Bone and blood interactions in human health and disease

Osteoprotegerin and RANKL in the pathogenesis of thalassemia-induced osteoporosis: New pieces of the puzzle

Human myeloma cells stimulate the receptor activator of nuclear factor-κB ligand (RANKL) in T lymphocytes: A potential role in multiple myeloma bone disease

Monoclonal antibodies against RANKL and sclerostin for myeloma-related bone disease: Can they change the standard of care?

Dickkopf-1 and sclerostin serum levels in patients with systemic mastocytosis

Anemia as a risk factor for low bone mineral density in postmenopausal Turkish women

Older men with anemia have increased fracture risk independent of bone mineral density

Chronic iron deficiency as an emerging risk factor for osteoporosis: A hypothesis

Imaging features of thalassemia

Bone demineralization in adult thalassaemic patients: Contribution of GH and IGF-I at different skeletal sites

Bone mineral density in prepubertal children with β-thalassemia: Correlation with growth and hormonal data

Iron distribution in thalassemic bone by energy-loss spectroscopy and electron spectroscopic imaging

Serum 1, 25 dihydroxyvitamin D and osteocalcin concentrations in thalassaemia major

Patterns of bone diseases in transfusion-dependent homozygous thalassaemia major: Predominance of osteoporosis and desferrioxamine-induced bone dysplasia

The "lively" cytokines network in β-thalassemia major-related osteoporosis

Zoledronic acid for the treatment of osteoporosis in patients with beta-thalassemia: Results from a single-center, randomized, placebo-controlled trial

Hematological diseases and osteoporosis

Effects of teriparatide retreatment in a patient with β-thalassemia major

Denosumab in transfusion-dependent thalassemia osteoporosis: A randomized, placebo-controlled, double-blind phase 2b clinical trial

Reduced bone mineral density in patients with haemophilia A and B in Northern Greece

Role of exercise and physical activity on haemophilic arthropathy, fall prevention and osteoporosis

Osteoporosis in haemophilia-an underestimated comorbidity? Haemophilia

Vitamin D deficiency and Osteoporosis in Hemophilia: An Underappreciated Risk

The role of sclerostin/dickkopf-1 and receptor activator of nuclear factor kB ligand/osteoprotegerin signalling pathways in the development of osteoporosis in patients with haemophilia A and B: A cross-sectional study

Factor VIII-von Willebrand factor complex inhibits osteoclastogenesis and controls cell survival

Bone density in haemophilia: A single institutional cross-sectional study

Long-term prophylaxis in severe haemophilia seems to preserve bone mineral density

Fracture risk in monoclonal gammopathy of undetermined significance

Fracture risk with multiple myeloma: A population-based study

Serum concentrations of DKK-1 correlate with the extent of bone disease in patients with multiple myeloma

Myeloma cells suppress bone formation by secreting a soluble Wnt inhibitor, sFRP-2

Monoclonal gammopathy of undetermined significance: A consensus statement

The clinical relevance and management of monoclonal gammopathy of undetermined significance and related disorders: Recommendations from the European Myeloma Network

Zoledronate is a potent inhibitor of myeloma cell growth and secretion of IL-6 and MMP-1 by the tumoral environment

Novel actions of bisphosphonates in bone: Preservation of osteoblast and osteocyte viability

Preclinical perspectives on bisphosphonate renal safety

A single-dose study of denosumab in patients with various degrees of renal impairment

Bortezomib inhibits human osteoclastogenesis

Anti-DKK1 mAb (BHQ880) as a potential therapeutic agent for multiple myeloma

Genetic deletion of Sost or pharmacological inhibition of sclerostin prevent multiple myeloma-induced bone disease without affecting tumor growth

High prevalence of fractures and osteoporosis in patients with indolent systemic mastocytosis

Prevalence and risk factors for fragility fracture in systemic mastocytosis

Prognosis in adult indolent systemic mastocytosis: A long-term study of the Spanish Network on Mastocytosis in a series of 145 patients

Serum levels of bone cytokines are increased in indolent systemic mastocytosis associated with osteopenia or osteoporosis

Bone involvement and osteoporosis in mastocytosis

Systemic mastocytosis and bone involvement in a cohort of 75 patients

Denosumab for the treatment of mastocytosis-related osteoporosis: A case series

Interferon alpha and pamidronate in osteoporosis with fracture secondary to mastocytosis

Teriparatide may accelerate the growth of a pre-existing malignant tumor in an elderly patient with osteoporosis: A case report

RANKL/RANK/OPG system beyond bone remodeling: Involvement in breast cancer and clinical perspectives

Elderly patients with non-Hodgkin lymphoma who receive chemotherapy are at higher risk for osteoporosis and fractures

Keinan-Boker, L. Hormone therapy and osteoporosis in breast cancer survivors: Assessment of risk and adherence to screening recommendations

Bone mineral density after adjuvant chemotherapy for premenopausal breast cancer

Effect of an aromatase inhibitor on BMD and bone turnover markers: 2-year results of the Anastrozole, Tamoxifen, Alone or in Combination (ATAC) trial (18233230)

Pamidronate to prevent bone loss during androgen-deprivation therapy for prostate cancer

Screening and management of osteoporosis in breast cancer patients on aromatase inhibitors

Implementation of osteoporosis screening guidelines in prostate cancer patients on androgen ablation

Practical guidance for the management of aromatase inhibitor-associated bone loss

Th17 functions as an osteoclastogenic helper T cell subset that links T cell activation and bone destruction

Anti-Sclerostin Antibody in Adults With Moderate Osteogenesis Imperfecta: Results of a Randomized Phase 2a

Osteoporosis in Inflammatory Arthritides: New Perspective on Pathogenesis and Treatment. Front. Med. 2020

Bone mineral density and frequency of osteoporosis in female patients with rheumatoid arthritis: Results from 394 patients in the Oslo County Rheumatoid Arthritis register

Prevalence and clinical prediction of osteoporosis in a contemporary cohort of patients with rheumatoid arthritis

Incidence of fractures among patients with rheumatoid arthritis: A systematic review and meta-analysis

Osteoporosis Pathophysiology, Epidemiology, and Screening in Rheumatoid Arthritis

Periarticular bone structure in rheumatoid arthritis patients and healthy individuals assessed by high-resolution computed tomography

Senescent T-Cells Promote Bone Loss in Rheumatoid Arthritis

Anti-citrullinated protein antibodies and high levels of rheumatoid factor are associated with systemic bone loss in patients with early untreated rheumatoid arthritis

Anti-citrullinated protein antibodies are associated with decreased bone mineral density: Baseline data from a register of early arthritis patients

Association of high titers of anticarbamylated protein antibodies with decreased bone mineral density in early arthritis patients

Effects of biological and targeted synthetic DMARDs on bone loss in rheumatoid arthritis

Conventional synthetic disease-modifying antirheumatic drugs and bone mineral density in rheumatoid arthritis patients with osteoporosis: Possible beneficial effect of leflunomide

Inhibition of tumor necrosis factor-alpha (TNF-alpha) in patients with early rheumatoid arthritis results in acute changes of bone modulators

Tocilizumab potentially prevents bone loss in patients with anticitrullinated protein antibody-positive rheumatoid arthritis

Abatacept might increase bone mineral density at femoral neck for patients with rheumatoid arthritis in clinical practice: AIRTIGHT study

The effect of low-dose methotrexate on bone mineral density in patients with early rheumatoid arthritis

Systemic evaluation of the relationship between psoriasis, psoriatic arthritis and osteoporosis: Observational and Mendelian randomisation study

Association of psoriasis and psoriatic arthritis with osteoporosis and pathological fractures

Osteoporosis in psoriatic arthritis: A cross-sectional study of an outpatient clinic population

Altered Bone Remodeling in Psoriatic Disease: New Insights and Future Directions

High prevalence of low bone mineral density in patients within 10 years of onset of ankylosing spondylitis: A systematic review

Ankylosing spondylitis is associated with an increased risk of vertebral and nonvertebral clinical fractures: A population-based cohort study

Long-Term Treatment with TNF-Alpha Inhibitors Improves Bone Mineral Density But Not Vertebral Fracture Progression in Ankylosing Spondylitis

A meta-analysis of secondary osteoporosis in systemic lupus erythematosus: Prevalence and risk factors

Predictors of fracture risk in patients with systemic lupus erythematosus

Osteoporotic fractures in patients with systemic lupus erythematosus and end stage renal disease

Lupus and fractures

Bone turnover markers in relation to vitamin D status and disease activity in adults with systemic lupus erythematosus

Inflammatory diseases and bone fragility

Glucocorticoid Exposure and Fracture Risk in a Cohort of US Patients With Selected Conditions

Lower P1NP serum levels: A predictive marker of bone loss after 1 year follow-up in premenopausal systemic lupus erythematosus patients

Prevalence and risk factors of low bone mineral density in patients with multiple sclerosis

Multiple sclerosis is associated with low bone mineral density and osteoporosis

BMI levels with MS Bone mineral density levels in adults with multiple sclerosis: A meta-analysis

Bone health in patients with multiple sclerosis relapses

Increased levels of IL-23 and osteopontin in serum and cerebrospinal fluid of multiple sclerosis patients

The effects of smoking on bone metabolism

Relationships between intestinal calcium absorption, serum vitamin D metabolites and smoking in postmenopausal women

Serum parathyroid hormone (PTH) levels in smokers and non-smokers. The fifth Tromsø study

Women and smoking: The effect of gender on the epidemiology, health effects, and cessation of smoking

Impact of smoking cessation on bone mineral density in postmenopausal women

Smoking, smoking cessation, and fracture risk in elderly women followed for 10 years

Disuse Osteoporosis: Clinical and Mechanistic Insights

Administration of Denosumab Preserves Bone Mineral Density at the Knee in Persons With Subacute Spinal Cord Injury: Findings From a Randomized Clinical Trial

Sclerostin Antibody Preserves the Morphology and Structure of Osteocytes and Blocks the Severe Skeletal Deterioration After Motor-Complete Spinal Cord Injury in Rats

Genetic approaches to metabolic bone diseases

Osteogenesis imperfecta

Two Rare Mutations in the COL1A2 Gene Associate with Low Bone Mineral Density and Fractures in Iceland

Current concepts in osteogenesis imperfecta: Bone structure, biomechanics and medical management

Mineral particle size in children with osteogenesis imperfecta type I is not increased independently of specific collagen mutations

Bone structure assessed by HR-pQCT, TBS and DXL in adult patients with different types of osteogenesis imperfecta

Increased intra-cortical porosity reduces bone stiffness and strength in pediatric patients with osteogenesis imperfecta

Reduced diaphyseal strength associated with high intracortical vascular porosity within long bones of children with osteogenesis imperfecta

Bisphosphonate therapy for osteogenesis imperfecta

Systematic review of the effect of denosumab on children with osteogenesis imperfecta showed inconsistent findings

Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture

Genome Sequencing Association Study of Low Bone Mineral Density Identifies New Susceptibility Loci in the Phase I Qatar Biobank Cohort

European guidance for the diagnosis and management of osteoporosis in postmenopausal women

Surgical treatment of osteoporotic fractures: An update on the principles of management

The effect of bottom profile dimples on the femoral head on wear in metal-on-metal total hip arthroplasty

The effect of osteoporosis and its treatment on fracture healing a systematic review of animal and clinical studies