key: cord-0964124-dn827k6n
authors: di Filippo, Luigi; Formenti, Anna Maria; Doga, Mauro; Pedone, Erika; Rovere-Querini, Patrizia; Giustina, Andrea
title: Radiological Thoracic Vertebral Fractures are Highly Prevalent in COVID-19 and Predict Disease Outcomes
date: 2020-10-21
journal: J Clin Endocrinol Metab
DOI: 10.1210/clinem/dgaa738
sha: 79e846f2620face602069e1580e891a8b5fd3d89
doc_id: 964124
cord_uid: dn827k6n

CONTEXT AND OBJECTIVE: COVID-19 has become the most relevant medical issue globally. Despite several studies that have investigated clinical characteristics of COVID-19 patients, no data have been reported on the prevalence of vertebral fractures (VFs). Since VFs may influence cardiorespiratory function and disease outcomes, the aim of this study was to assess VFs prevalence and clinical impact in COVID-19. DESIGN AND PATIENTS: This was a retrospective cohort study performed at San Raffaele Hospital, a tertiary health care hospital in Italy. We included COVID-19 patients for whom lateral chest x-rays at emergency department were available. VFs were detected using a semiquantitative evaluation of vertebral shape on chest x-rays. RESULTS: A total of 114 patients were included in this study and thoracic VFs were detected in 41 patients (36%). Patients with VFs were older and more frequently affected by hypertension and coronary artery disease (P < 0.001, P = 0.007, P = 0.034; respectively). Thirty-six (88%) patients in VFs+ group compared to 54 (74%) in VFs− group were hospitalized (P = 0.08). Patients with VFs more frequently required noninvasive mechanical ventilation compared with those without VFs (P = 0.02). Mortality was 22% in VFs+ group and 10% in VFs− group (P = 0.07). In particular, mortality was higher in patients with severe VFs compared with those with moderate and mild VFs (P = 0.04). CONCLUSIONS: VFs may integrate the cardiorespiratory risk of COVID-19 patients, being a useful and easy to measure clinical marker of fragility and poor prognosis. We suggest that morphometric thoracic vertebral evaluation should be performed in all suspected COVID-19 patients undergoing chest x-rays.

Since only about one-third of VFs are actually clinically diagnosed using the historical (anamnestic questionnairebased) approach, radiological and morphometric approaches have emerged as the gold standard to assess the true prevalence and incidence of VFs in the general population and high-risk patients (20, 21) . Interestingly, morphometric VFs can be detected also on lateral chest x-rays (21, 22) .

To date, no previous data have been reported on VF prevalence in patients affected either by COVID-19 or by other coronavirus diseases, such as SARS, MERS, and Ebola. The aim of this study was to investigate VFs in COVID-19 patients on lateral chest x-rays performed at admission in the Emergency Department (ED), and to evaluate their possible influence on clinical outcomes in these patients.

This retrospective cohort study was part of the COVID-BioB study, which was a large observational investigational study performed at San Raffaele University Hospital, a tertiary health care hospital in Milan, Italy. The study protocol was approved by the Hospital Ethics Committee (protocol no. 34/int/2020).

We included only patients aged ≥18 years with a confirmed diagnosis of COVID-19 who were admitted to our ED. Confirmed COVID-19 was defined as positive real-time reverse-transcriptase polymerase chain reaction (RT-PCR) from a nasal and/or throat swab together with signs, symptoms, and radiological findings suggestive of COVID-19 pneumonia. Patients admitted for other diseases and subsequently diagnosed with superimposed SARS-CoV-2 infection, as well as patients acutely treated with glucocorticoids before hospitalization for their pulmonary condition, were excluded. We included in our evaluation only patients for whom lateral chest x-rays at ED admission were available. Only lateral chest x-rays that allowed a high-quality assessment were used for the analyses, excluding exams in which pneumonia opacities or low quality-images due to patient intrinsic characteristics (positions and severe scoliosis) prevented a correct evaluation. In particular, we used only x-rays in which all the thoracic tract of T4 to T12 vertebrae was well viewable and assessable.

Data were collected from medical chart review or directly by patient interview and entered in a dedicated electronic case record form (eCRF) specifically developed for the COVID-BioB study, evaluated and approved by Hospital Ethics Committee. Prior to the analysis, data were crosschecked with medical charts and verified by data managers and clinicians for accuracy. The following variables were collected: age; gender; comorbidities (identified in medical history by patient or caregivers or referred to in previous medical documentation, including history of hypertension, diabetes mellitus, coronary artery disease (CAD), chronic kidney disease, osteoporosis, active neoplasms, and severe neurological disabilities); body mass index (BMI, calculated as the ratio of weight in kilograms (kg) divided by height in squared meters); PaO2/FiO2 (calculated as the ratio between the arterial partial pressure of oxygen measured on arterial blood gas test and the fraction of inspired oxygen); ionized serum calcium (measured on arterial blood gas test); estimated glomerular filtration rate (eGFR, as estimated by the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equation and expressed as mL/ min/L·73m 2 ); lactate dehydrogenase (LDH, U/L); and highsensitivity C-reactive protein (CRP, mg/L); treatments on ED admission; and clinical outcome (discharge from ED or hospital ward, admission to intensive care unit [ICU] during hospital stay, hospital length of stay, needs for noninvasive mechanical ventilation, and death).

Thoracic VFs were detected on lateral chest x-rays using a qualitative and semiquantitative assessment and evaluation of vertebral shape (21, 22) . Using a translucent digitizer and a cursor, 6 points were marked on each vertebral body to describe vertebral shape. Anterior, middle, and posterior vertebral heights were measured, and height ratios (anterior/posterior, middle/posterior) were calculated for each vertebral body from T4 to T12. According to the semiquantitative score method initially proposed by Genant et al (23) , fractures were defined as mild, moderate, and severe based on height ratio decreases of 20% to 25%, 25% to 40%, and up to 40%, respectively. Two experienced physicians (M.D., L.D.F.) were blinded to the underlying diagnosis and were then asked to perform the analyses. They also visually assessed VFs (which had to be concordantly assigned by the 2 physicians) and the superior and inferior endplate of the vertebral bodies to exclude artifacts and overestimation of VFs (24, 25) .

The Black algorithm was applied to confirm morphometric diagnosis of VFs. To this end, the height ratios in each examined vertebra were used to calculate a fracture threshold (26, 27) , and the fracture threshold was calculated as 85% of the arithmetical mean of anterior/posterior height ratio (26, 27) .

The interobserver agreement between the 2 physicians for the identification of vertebral fractures was analyzed using the kappa score, ranging from 0 (no agreement) to 1 (complete agreement) where values lower than 0.6 were considered moderate and those greater than 0.8 strong agreement.

Descriptive statistics were obtained for all study variables. Continuous variables were expressed as medians [25th to 75th percentile]. Categorical variables were summarized as counts and percentages. Categorical variables were compared by using the Fisher exact test or χ2 test, and continuous variables were compared using the Mann-Whitney U test. All statistical tests were 2-sided. A P value of < 0.05 was considered statistically significant. Statistical analysis was conducted using IBM SPSS Statistics (IBM SPSS Statistics for Windows, Version 23.0. Armonk, NY).

A total of 114 COVID-19 patients with evaluable lateral chest x-rays were included in the study. Approximately three-quarters of patients were male (74.6%), and the median age was 57 (51-71) years. Patient characteristics upon admission at ED are summarized in Table 1 .

In our population, the main comorbities were history of arterial hypertension (39.5%), followed by CAD (12.3%), diabetes mellitus (10.5%) and chronic kidney disease (9.6%). Osteoporosis was previously diagnosed in only 3 patients (2.8%). Five patients (4.4%) were on chronic glucocorticoid medication, 4 (3.5%) on vitamin D supplements and 1 (0.9%) on bisphosphonate therapy.

Ninety patients (78.9%) were hospitalized after initial evaluation in ED, and 13 of these (11.6%) were admitted to the ICU during hospitalization, while 16 (14.5%) patients died.

Thoracic VFs on lateral chest x-rays at ED admission were detected in 41 patients (36%) (Fig. 1) . A total of 65 VFs were detected; according to Genant classification, 39 of these (60%) were classified as mild, 21 (33.3%) as moderate, and 5 (7.7%) as severe (Figs 1 and 2; Table 2) Average height ratio and average fracture threshold, according to the Black algorithm, were 0.931 and 0.791, respectively (Table 2) . Therefore, the number of vertebral fractures detected applying this algorithm was the same detected by the semiquantitative method of Genant.

There were 28/41 (70.7%) patients with at least one mild vertebral fracture, 18/41 (43.9%) with at least one moderate, and 5/41 (12.2%) with at least one severe. In 19 of 41 (46.3%) fractured patients, multiple VFs were detected. Among these 19 patients, we found 6 (31.6%) patients with 2 mild VFs, 1 (5.3%) patient with 3 mild VFs, and 2 (10.5%) patients with 2 moderate VFs. In 7 (36.8%) patients, both mild and moderate VFs and in 3 (15.8%) both moderate and severe VFs were found; thus, in order to evaluate impact of VFs on outcomes, those with both mild and moderate VFs were assigned to the "moderate" group and those with both moderate and severe fractures were assigned to the "severe" group.

The interobserver agreement between the 2 physicians for the identification of mild, moderate, and severe vertebral fractures was k = 0.84, k = 0.87, and k = 1, respectively. No differences were found between VFs+ and VFs− group with respect to sex distribution, BMI, or clinical and biochemical parameters evaluated in the ED (Table 3) . Regarding the prevalence of comorbidities, arterial hypertension and CAD were found statistically more frequently in VFs+ group (arterial hypertension: VFs+ 56% vs VFs− 30%, P = 0.007; CAD: VFs+ 22% vs VFs− 7%, P = 0.034). VFs+ patients were also older compared to VFs− (VFs+: 68 [55.5-76] years vs VF−: 54 [48] [49] [50] [51] [52] [53] [54] [55] [56] [57] [58] [59] [60] [61] [62] [63] [64] years, P < 0.001) ( Fig. 3 ; Table 3 ).

Serum ionized calcium analysis from arterial blood gas tests performed in the ED was collected in 78 patients; hypocalcemia, defined as a calcium value below 1.18 mmol/L, was found in 60 patients (87.2%). No CRP, C-reactive protein; eGFR, estimated glomerular filtration rate, calculated using the CKD-EPI equation; IQR, interquartile range; LDH, lactate dehydrogenase; PaO2/FiO2 ratio, ratio between the arterial partial pressure of oxygen measured on arterial blood gas analysis and the fraction of inspired oxygen; SpO2, peripheral oxygen saturation. a Only active neoplasms were included reported In lateral chest x-rays it is possible to identify a T11 mild VF with a height ratio decrease of 22% using posterior and anterior vertebral heights. In frontal view no COVID-19 pneumonia signs were present. b) In lateral chest x-rays it is possible to identify a T6 moderate VF with a height ratio decrease of 27% and a T7 mild VF with a height ratio decrease of 21%, using posterior and anterior vertebral heights. In frontal view it is possible to see bilateral . ground-glass opacities related to COVID-19 infection. c) In lateral chest x-rays it is possible to identify a T11 severe VF with a height ratio decrease of 55% and a T12 moderate VF with a height ratio decrease of 34%, using posterior and anterior vertebral heights. In frontal view is possible to see bilateral ground-glass opacities and lung consolidations related to COVID-19 infection. d) In lateral chest x-rays it is possible to identify a T12 severe VF with a height ratio decrease of 42% using posterior and middle vertebral heights. In frontal view is possible to see slight bilateral ground-glass opacities related to COVID-19 infection.

significant differences were found between VFs+ and VFs− group in ionized calcium levels and rate of hypocalcemia (P = 0.16, P = 0.54; respectively) ( Table 4) .

Thirty-six (88%) patients in the VFs+ group compared with 54 (74%) patients in the VFs− group were hospitalized (P = 0.08) ( Table 5 ). Four (11%) patients in the VFs+ group and 9 (12.5%) patients in the VFs− group were admitted to the ICU during hospitalization (P = 0.76) ( Table 5) . Patients with VFs more frequently required noninvasive mechanical ventilation (NIMV) compared to those without VFs (48.8% vs 27.4%, P = 0.02) ( Table 5 ). No differences were found about hospital length of stay (Table 5) . Mortality was 22% in the VFs+ group and 10% in the VFs− group (P = 0.07) ( Table 5 ). In particular, mortality was statistically higher in patients with severe VFs compared to those with moderate and mild VFs (60%, 7%, 24% in severe, moderate, and mild VFs group, respectively, P = 0.04), despite no statistically significant differences regarding clinical and laboratory characteristics found among these 3 groups (Tables 5 and 6 ).

To the best of our knowledge, this is the first study assessing the presence and the clinical impact of VFs in COVID-19 patients. We found that VFs were highly prevalent in our study population, as up to 36% of patients presented a vertebral deformity, although only 3% had a previous diagnosis of osteoporosis reported in their past medical history. Vertebral fracture prevalence detected in our study population was much higher as compared with epidemiological data reported in previous studies on general populations, despite the fact that only the thoracic tract was evaluated.

In recent studies evaluating European women aged 50 years and over, the incidence of new VFs was reported in 10.7/1000 person-years and prevalence of morphometric VFs ranged from 18% to 26% (28, 29) . Although osteoporosis is typically identified as a health issue only in postmenopausal women, we have found a high prevalence of VFs also in male patients. VFs were detected in 35% of COVID-19 male patients and in 37% of female patients, without any significant difference related to gender in prevalence of VFs. To date, underdiagnosis of osteoporosis and VFs in male patients remains a critical medical issue, despite recent evidence with several reports of significant data regarding this topic. The European Vertebral Osteoporosis Study revealed that 8% to 20% of men aged 50 to 79 years had at least one VF, and in the United States the incidence of VFs in osteoporotic men had been estimated to be 15.3 and 33.4 per 100 000 person-years in patients aged 65 to 74 years and >75 years, respectively (30, 31) . Nevertheless, the impact of VFs in our COVID-19 population seems to exceed that expected in the general population, particularly the male population, beyond this previously reported issue of underdiagnosis. Nevertheless, the complete agreement of VF detection based on the Black algorithm and the Genant method, which was previously reported (27), does not seem to support the hypothesis of a methodological issue potentially leading to overestimation of (mild) VFs due to false positives in our study. In fact, there is also an increasing number of pathological conditions known to cause secondary osteoporosis and fragility fractures similarly in women and men, including long-term corticosteroid therapy, active acromegaly, and type 1 and type 2 diabetes mellitus (32) (33) (34) (35) (36) (37) . The high prevalence of thoracic VFs in our severe COVID-19 patients first admitted to the ED and successively hospitalized could be explained by possible VF influence on respiratory function of affected patients (although an objective measure of the degree of kyphosis was not available).

It has been previously reported that prevalent VFs with decreased bone mineral density (BMD) are associated with an increased risk of pneumonia and impaired respiratory function including restrictive pulmonary dysfunction, decrease in vital capacity, FEV1 (forced expiratory volume in the first second), and inspiratory time in patients without previous pulmonary diseases (18, 19, 38, 39) .

Not surprisingly, in our cohort, hypertension and CAD were found to be more prevalent in patients with VFs. Besides the possible impact of older age on this association, over the recent years, there has been growing evidence to suggest the existence of close correlation between hypertension, cardiac and vascular disease, and skeletal fragility. Recent findings showed an association between cardiovascular disease (CAD, cerebrovascular disease, peripheral atherosclerosis, heart failure) and high Framingham risk score with lower BMD and major osteoporotic fracture incidence in men and women (40) (41) (42) (43) . Mechanistically, osteoprotegerin, expressed in endothelial cells with a pivotal role in vascular calcification and osteoporosis, may be associated with vascular dysfunction promoting leukocyte adhesion to endothelial cells by inducing expression of VCAM-1, ICAM-1, and E-selectin (44, 45) .

In our study, the overall mortality rate was found to be doubled although not statistically different in patients with vs without VFs. However, we found it to be significantly higher in patients with severe VFs as compared to those with mild and moderate VFs without significant differences in age distribution between groups, although fractured patients as a whole were older than not fractured subjects. NIMV requirement was found to be statistically higher in patients with vs without VFs, confirming the possible negative influence of VFs on respiratory function, although no significant differences were found regarding hospitalization or ICU admission in patients with and without VFs.

Our findings are consistent with previous literature that identified an association between VFs and increased mortality, findings not only explained by advanced age, general health, and concurrent chronic diseases (17, (46) (47) (48) . Therefore, due to the relationship between older age (which was associated with VFs in multivariate analysis although not correlated with fracture severity), presence of cardiovascular disease and osteoporosis, and the negative influence of VFs on respiratory function, our data are consistent with the concept that VFs and their severity can be an objective clinical marker of frailty and negative prognosis in patients with COVID-19. Moreover, since the high prevalence of VFs in our patients may be associated with poor health status and in turn underlie the higher risk and severity of COVID-19, bone centers could be hypothesized to have a possible role in identifying patients with increased susceptibility to the viral pandemic. No significant differences in the rate of hypocalcemia between fractured vs nonfractured patients were found. This may be due to the widespread presence of hypocalcemia in our study population, which confirms findings from previous reports by our and several other groups (9, (49) (50) (51) (52) . Because in Italy there is a very high prevalence of hypovitaminosis D and since low circulating levels of vitamin D have also been correlated with disease severity, it cannot be excluded that the very high prevalence of VFs and hypocalcemia observed could be due to this condition (9, (49) (50) (51) (52) (53) (54) (55) (56) (57) .

Limitations of our study are the retrospective nature, which does not allow us to evaluate the timing of VFs; the limited number of enrolled patients due to the huge pressure on EDs, which did not allow lateral chest x-rays to be performed in many patients; and the lack of a BMD evaluation or vitamin D level assessment to better characterize bone metabolic status. The higher mortality rate in our patients with severe as compared to mild and moderate VFs should be interpreted with caution due to the low number of patients affected by severe VFs and needs to be confirmed in larger studies. Moreover, we could not evaluate possible influence of height reduction on disease outcomes and respiratory function since only height at hospital admission was available. Finally, we have only evaluated the thoracic spine. Therefore, despite thoracic VFs being the type most commonly observed in osteoporosis, our finding is likely to be an underestimate.

These limitations aside, this is the first study that investigated skeletal fragility in COVID-19 patients.

Pathophysiologically, it can be hypothesized that VFs in our population could be linked to increased combined cardiorespiratory risk since they may be associated with cardiovascular comorbidities but also predispose to respiratory failure and infection. Clinically, the results of our study demonstrate that VFs are one of the most frequent comorbidities in severe SARS-CoV-2 infection, almost reaching the level of one of the few clinical features which has been consistently shown to be strongly correlated with COVID-19 risk and prognosis, such as arterial hypertension with which VFs correlate well and with a much higher prevalence than other frequently reported COVID-19 comorbidities such as CAD, diabetes mellitus, and chronic kidney disease (1, 2) . Moreover, VFs were clinically meaningful, associating with a doubling in mortality risk, which was significantly higher in patients with severe as compared to mild and moderate VFs. It is interesting to note that our data confirm the hypothesis recently published by Napoli et al (7) who properly warned the medical community about the high likelihood of an increased risk of skeletal fragility and osteoporotic fracture with potential huge consequences on overall health status and recovery of affected patients. Our data from the field reinforce the need of implementing previously published recommendations concerning the importance of bone fragility care during the COVID-19 pandemic with at least those patients who are already treated with antiosteoporotic drugs maintaining their adherence to treatments including vitamin D (7, 57) , which have also been suggested very recently to have no relevant predisposing effect on COVID-19 (58) . Moreover, continuity of care should also include bone density monitoring (59), despite very restricted access to clinical facilities during the COVID-19 pandemic (7). Finally, all patients with fractures should start antiresorptive treatment right away, even during hospital stay (60) . This recommendation should be also strengthened in COVID patients with fractures (7).

In conclusion, since thoracic VFs are easy to measure, associate with age, and integrate the cardiorespiratory risk of COVID-19 patients, they are a good marker of patient fragility and poor prognosis and we suggest that morphometric vertebral x-rays evaluation should be performed in all patients with suspected COVID-19.

Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia

the Northwell COVID-19 Research Consortium. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City Area

New understanding and treatments for osteoporosis

Proinflammatory cytokines and osteoporosis

Secondary osteoporosis: pathophysiology & diagnosis

Glucocorticoidinduced osteoporosis: pathophysiology and therapy

Managing fragility fractures during the COVID-19 pandemic

Induction of proinflammatory cytokines (IL-1 and IL-6) and lung inflammation by Coronavirus-19 (COVI-19 or SARS-CoV-2): anti-inflammatory strategies

Hypocalcemia is highly prevalent and predicts hospitalization in patients with COVID-19

The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): the perspectives of clinical immunologists from China

Malnutrition and nutritional therapy in patients with SARS-CoV-2 disease

Endocrine and metabolic aspects of the COVID-19 pandemic

Osteoporosis management in the era of COVID-19

Endocrinology in the time of COVID-19: management of calcium metabolic disorders and osteoporosis

Osteoporosis in the age of COVID-19

Melton LJ 3 rd . Incidence of clinically diagnosed vertebral fractures: a population-based study in

Association between vertebral fracture and increased mortality in osteoporotic patients

Restrictive pulmonary dysfunction is associated with vertebral fractures and bone loss in elderly postmenopausal women

Relationship between vertebral fracture burden, height loss, and pulmonary function in postmenopausal women with osteoporosis

New advances in imaging osteoporosis and its complications

Risk of vertebral fractures in hypoparathyroidism

High Prevalence of Radiological Vertebral Fractures in Patients With TSH-Secreting Pituitary Adenoma

Comparison of semiquantitative visual and quantitative morphometric assessment of prevalent and incident vertebral fractures in osteoporosis The Study of Osteoporotic Fractures Research Group

Comparison of methods for the visual identification of prevalent vertebral fracture in osteoporosis

Osteoporotic Vertebral Fracture Prevalence Varies Widely Between Qualitative and Quantitative Radiological Assessment Methods: The Rotterdam Study

A new approach to defining normal vertebral dimensions

Similar prevalence of vertebral fractures despite different approaches to define reference data

European Prospective Osteoporosis Study (EPOS) Group. Incidence of vertebral fracture in europe: results from the European Prospective Osteoporosis Study (EPOS)

Worldwide prevalence and incidence of osteoporotic vertebral fractures

The prevalence of vertebral deformity in european men and women: the European Vertebral Osteoporosis Study

Fracture incidence in a large cohort of men age 30 years and older with osteoporosis

High prevalence of asymptomatic vertebral fractures in post-menopausal women receiving chronic glucocorticoid therapy: a cross-sectional outpatient study

Increased prevalence of radiological spinal deformities in active acromegaly: a cross-sectional study in postmenopausal women

Acromegaly and Vertebral Fractures: Facts and Questions

Vertebral fractures in males with type 2 diabetes treated with rosiglitazone

Systematic review of type 1 and type 2 diabetes mellitus and risk of fracture

Mechanisms of anabolic therapies for osteoporosis

Respiratory complications and mortality risk associated with thoracic spine injury

Risk of pneumonia after vertebral compression fracture in women with low bone density: a population-based study

Association between hypertension and fragility fracture: a longitudinal study

Risk of major osteoporotic fracture after cardiovascular disease: a population-based cohort study in Taiwan

High osteoporotic fracture risk and CVD risk co-exist in postmenopausal women

Prevalence of thoracic vertebral fractures in hospitalized elderly patients with heart failure

Osteoporosis-a risk factor for cardiovascular disease?

Osteoprotegerin increases leukocyte adhesion to endothelial cells both in vitro and in vivo

Mortality risk associated with low-trauma osteoporotic fracture and subsequent fracture in men and women

Mortality associated with vertebral deformity in men and women: results from the European Prospective Osteoporosis Study (EPOS)

Vertebral fractures and mortality in older women: a prospective study. Study of Osteoporotic Fractures Research Group

Severe hypocalcemia in a thyroidectomized woman with Covid-19 infection

Low levels of total and ionized calcium in blood of COVID-19 patients

Prevalence and predictive value of hypocalcemia in severe COVID-19 patients

Serum calcium as a biomarker of clinical severity and prognosis in patients with coronavirus disease

COVID-19 and endocrine diseases. A statement from the

25-hydroxyvitamin D concentrations are lower in patients with positive PCR for SARS-CoV-2

Preventing a covid-19 pandemic Can high prevalence of severe hypovitaminosis D play a role in the high impact of Covid infection in Italy?

The role of vitamin D in the prevention of coronavirus disease 2019 infection and mortality

Mechanisms in endocrinology: vitamin D and COVID-19

Are women with osteoporosis treated with denosumab at risk of severe COVID-19? Endocrine

The ability of a single BMD and fracture history assessment to predict fracture over 25 years in postmenopausal women: the study of osteoporotic fractures

Secondary fracture prevention: consensus clinical recommendations from a multistakeholder coalition

The authors wish to thank Dr. Stefano Frara for critically reviewing the manuscript. This study was partially supported by GIOSEG (Glucocorticoid induced Osteoporosis Skeletal Endocrinology Group).Author Contributions: All authors contributed equally.

Correspondence and Reprint Requests: Prof. Andrea Giustina, MD, Division of Endocrinology, IRCCS San Raffaele Hospital, via Olgettina 60, 20132 Milano, Italy. E-mail: giustina.andrea@hsr.it.Disclosure Summary: The authors have nothing to disclose. The work submitted for publication is original and has not been published other than as an abstract or preprint in any language or format and has not been submitted elsewhere for print or electronic publication consideration.Data Availability: All data generated and analyzed during this study are included in this published article.