key: cord-0704109-o1hxoasp
authors: Upadhyaya, Gaurav K.; Iyengar, Karthikeyan; Jain, Vijay K.; Vaishya, Raju
title: Challenges and strategies in management of osteoporosis and fragility fracture care during COVID-19 pandemic
date: 2020-06-02
journal: J Orthop
DOI: 10.1016/j.jor.2020.06.001
sha: a344bfe97206b814b66d64a47661b369739fa6b6
doc_id: 704109
cord_uid: o1hxoasp

BACKGROUND: COVID-19 has resulted in restriction of face to face consultations and mechanisms to access health care. Osteoporosis and fragility fractures forms a significant proportion of adult trauma and orthopaedic workload even during the pandemic. AIMS: We assess the challenges and strategies used in the management of osteoporosis and fragility fracture care during the COVID-19 pandemic. METHODS: We have done a comprehensive review of the literature using suitable keywords on the search engines of PubMed, SCOPUS, Google Scholar and Research Gate in the first week of May 2020 on developments and guidance during the current COVID-19 pandemic. RESULTS: Osteoporosis and fragility fractures management has been hampered by lock down and infection transmission strategies used to contain the COVID-19 pandemic. Access to diagnostic tests, treatment facilities with the need to use clinical and prediction tools to guide management Telemedicine has an evolving role. CONCLUSION: Osteoporosis and fragility fractures in elderly individuals pose a real challenge for an appropriate diagnosis and management, during the COVID-19 pandemic. A clinical decision along with use of clinical prediction tools for osteoporosis should be used to direct treatment. Obligatory fractures such as hip fractures require operative intervention. Non-obligatory fractures such as distal radius fractures can be managed conservatively with use of telemedicine applications in monitoring both types of patients.

COVID-19 pandemic has had a significant effect on how organizations deliver health care [1] . Trauma and orthopaedic surgery services has been reorganized with significant cancellation of elective surgery to focus on acute clinical priorities on the coronavirus frontlines [2] . Fragility fractures forms a significant proportion of adult trauma and orthopaedic workload even during the pandemic [3] . During the lockdown period the number of injuries due to motor vehicle accidents has come own [4] but we are still receiving low energy fractures around the hip like neck femur and intertrochanteric fractures, due to osteoporosis. The vertebral fractures due to osteoporosis can lead to chronic pain and deformity with advanced disease. Hip and spine fractures in the elderly are associated with increased mortality, reduction in quality of life, and functional limitations along with substantial economic burden to the health sector which further compromises the COVID -19 related treatment [5] .Therapeutic interventions that mitigate fragility fracture in era of COVID-19 are, therefore, essential for reducing the consequences in the future. A patient with osteoporosis requires complete care, multidisciplinary intervention, and patient centric rehabilitation plan; all these will be affected due to COVID-19 [6] .

In this comprehensive review we have assessed the impact of challenges posed by COVID - 19 in managing osteoporosis and fragility fractures and strategies used to mitigate them.

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Osteoporosis is a public health concern all over the world. It is a multifactorial, metabolic bone disease which is characterized by low bone mass, normal mineralization and abnormal bone micro-architecture [7] . This disruption of bone microarchitecture causes subsequent and significant increase in the risk for fractures. Osteoporosis affects approximately over 200 million people worldwide. In India, there are around 50 million individuals with osteoporosis or low bone mass [8] . In India; more than 4.5 million women above the age of 60 years suffered fracture spine and more than 250,000 people sustain a hip fracture every year due to osteoporosis [9] . Similarly, the total number of fragility fractures in the EU6 is estimated to increase from 2.7 million in 2017 to 3.3 million in 2030; an increase of 23.3% [10] .

There are several factors including social and financial reasons which can contribute to osteoporosis in India. These are (i) low intake of Calcium and Vitamin D supplements (ii) unequal distribution milk and their products, (iii) predominantly vegetarian diet, with phytates and oxalates fibre-rich Indian food, (iv) avoidance of sunlight exposure, (v) life style change, (vi) lack of physical, (vii) Glucocorticoid consumption for different reasons on a long-term, (viii) Genetic differences, (ix) Poor level of awareness and (x) government apathy to bone health [11, 12] . These factors are further affected by lock down measures, with people staying indoors at home and may be facing poor supply of milk products due to supply and distribution restraints [13] .With an increase in life expectancy, the percentage of ageing population is increasing and so does the prevalence of osteoporosis and fragility fractures.

Recently there has been emerging and growing evidence that Vitamin D also protect against COVID-19 and to the severity of the disease. The plausible mechanisms include induction of cathelicidins and defensin proteins by vitamin D that can decreases the viral replication rates and COVID-19 related cytokine storm that produce the inflammation in lining of the lungs, leading to pneumonia [14] .

Fragility fractures are fractures that result from mechanical forces that would not ordinarily result in fracture, known as low-level (or 'low-energy') trauma, quantified by The World

Health Organization (WHO) as forces equivalent to a fall from a standing height or less. In fact a fragility fracture may be defined as a pathological fracture that results from minimal trauma (e.g. a fall from a standing height) or no identifiable trauma at all [15] . The fragility fracture thus is both a sign and a symptom of osteoporosis. Fragility fractures most commonly affect vertebrae, proximal femur and distal radius; however any bone can be affected by it [16] . There is a likely connection between COVID-19 infection and fragility hip fracture in elderly patients. Fragility fracture can be induced as a result of a fall from a standing due to by fatigue and weakness caused by COVID-19 disease. Therefore COVOID-coronavirus pandemic [17] . Osteoporosis is a major risk factor for fragility fractures [16] .

Fragility fractures can be divided into obligatory fractures which require surgery and nonobligatory fractures which can be managed by conservative means [18, 19] .

The diagnosis of osteoporosis relies on the quantitative assessment of bone mineral density (BMD), usually by central dual energy X-ray absorptiometry (DXA) BMD at the femoral neck provides the reference site. Osteoporosis is defined by the World Health Organization by comparing a patient's bone mineral density (BMD) to that of patients at the time of peak bone mass (T-score). Dual energy X-ray absorptiometry (DXA) scan to assess bone mineral density (BMD) is considered as a gold standard for the diagnosis of osteoporosis. It is defined as a value for BMD 2.5 SD or more below the young female adult mean (T-score less than or equal to -2.5SD). Severe osteoporosis (established osteoporosis) describes osteoporosis in the presence of 1 or more fragility fractures.

• Normal bone mineral density is within 1 SD • Low bone mass (osteopenia) is between 1 SD and 2.5 SD below mean peak bone mass • Osteoporosis is more than 2.5 SD below mean peak bone mass.

However in this situation of COVID-19 pandemic, DEXA scan for BMD assessment is not easily feasible because of the lockdown, travel restrictions and closure of routine services in the hospitals [20] . The doctors need to keep a conscious awareness of osteoporosis in their patients and should not stop diagnosing people at risk or those who present with fractures even when they cannot perform full screening tests [21] .

Therefore it increases our dependence on clinical history and osteoporosis related fracture prediction tools. History should be taken to know about any of previous fracture; the Colles' fracture is an early and sensitive indicator of skeletal fragility, predisposing the patient to additional fractures, in particular of the hip [22] .

Clinical prediction tools such as Fracture Risk Assessment Tool (FRAX), Osteoporosis selfassessment tool and the Khon Kaen Osteoporosis study score for assessing people at risk for osteoporosis [23, 24, 25] .

Plain radiographs still are helpful and should be taken to recognize osteoporosis. Traditional radiology can possibly diagnose osteoporosis fractures in the most commonly involved sites (spine, pelvis, distal radius, proximal femur and humerus,). Vertebral fractures due to bone fragility can be identified easily with vertebral morphometry. The spinal height reduction, make it possible to identify wedge-shaped, biconcave, total vertebral collapse fractures [22] Challenges in medical therapy for osteoporosis during the pandemic Medical management of osteoporosis includes general and pharmacological interventions.

General management includes assessment of the risk of falls and their prevention.

Maintenance of mobility and correction of nutritional deficiencies, particularly of calcium, vitamin D and protein, should be advised. Intakes of at least 1000 mg/day of calcium, 800 IU of vitamin D and of 1 g/kg body weight of protein can be recommended. To reduce the risk of infection, it is recommended that people at risk of COVID-19 should take 10,000 IU/d of vitamin D3 for a few weeks, followed by 5000 IU/d [14] . An adequate intake of calcium rich diet including milk and its derivatives, almonds, cabbage, spinach, turnips and pulses should also be advised. For reduction in fracture risk, particularly in the elderly, the supplementation of calcium should be given who cannot afford nor have availability of these products in their area. Vitamin D is present in animal fats, fish, milk, and dairy products. The patients should be encouraged to consume these products and have walk for at least 30min in their courtyard for proper sun exposure.

Osteo-anabolic agents. Anti-restorative drugs include Bisphosphonates, Denosumab,

Teriparatide and Strontium Ranelate.

The low cost of generic alendronate, which has a broad spectrum of anti-fracture Efficacy makes this the first line treatment in the majority of cases [26] . In individuals who are intolerant of alendronate or in whom it is contraindicated, other Bisphosphonates, strontium ranelate or raloxifene may provide appropriate treatment options However, intravenous use of Zoledronate or Ibandronate in bisphosphonate-naïve or pretreated patients is associated with acute phase reaction with fever and myalgia. This flu like reaction may occur in up to 50% of patients [27, 28] . The possibility of this flu like reaction which imitate clinical features of COVID-19 infection during the pandemic should be discussed with patients. A laboratory evaluation should be advised to the patients with impaired renal function and for those at higher risk of developing hypocalcaemia before IV administration of these drugs, which is difficult to arrange in COVID-19 settings. Further these patients require short hospitalization for observation during IV infusion which will be difficult in current scenario when the hospitals are flooded with COVID-19 patients and the transportation is limited in many areas. Additionally, due to the lockdown the demand and supply of these drugs may be affected [20] .

The patients who are taking parenteral bisphosphonates therefore may be advised for telemedicine consultations with their doctors and to start with oral bisphosphonates without any delay, but with all the precautions; preferably with Alendronate, as it is well studied, and has a good bone binding affinity and safety profile than other oral drugs in this group [26] .

Patients who are already receiving subcutaneous Denosumab every 6 months may face a difficult choice to continue the treatment without going to healthcare facility. The risk of adverse events of COVID -19 infection increases with use of Denosumab which should be discussed with the patients [29] . Furthermore, there may be rapid bone loss within one year of discontinuation of Denosumab and risk of vertebral fragility fractures is increased [30, 31, 32] . Discontinuation of Denosumab should be strongly discouraged by the clinician and patients may be started on oral bisphosphonates. Home visit of health care personnel can be planned for drug administration. Telemedicine services may prove to be helpful in these patients providing video tutorials and education on self-administration of subcutaneous injections of this drug [33] .

The high cost of parathyroid hormone peptides restricts their use to those at very high risk, particularly for vertebral fractures. It is also noted that the patients receiving subcutaneous Teriparatide injection treatment can be delayed up to the duration of 3 months [34] . If more delay is expected in such patients, then they should be started on oral bisphosphonates on temporary basis till they are able to get a Teriparatide prescription.

With limited evidence, there is concern that COVID-19 infection may be associated with hypercoagulable condition. Estrogen and Selective Estrogen Receptor Modulators such as Raloxifene should be used with caution since these drugs mildly increase the thrombotic risk [35, 36] .

Fragility hip fractures are usually sustained in the elderly people who have associated comorbidities. Obligatory fractures such as hip and vertebral fractures with neurological deficit require operative intervention. Patients should be screened and tested for COVID-19 at the emergency setup. All precautions pertaining to COVID-19 should be taken whilst managing patient in the emergency department and on in-patient wards until reports are available. If COVID testing is not possible then a 'Human immunodeficiency virus HIV model', as suggested by Jain V et al [37] can be adopted in the operative management of these patients and every patient should be treated as COVID-19 positive until proved otherwise [37] .

Confirmed or suspected COIVD-19 infection in these patients is not a reason to postpone or cancel hip surgery. British Geriatric Society (BGS) guidelines aim to promote prompt (less than 24 hrs) consultant-delivered surgical and anaesthetic care where possible [18, 19] . As recommended by the BGS guidelines, a multidisciplinary approach still remains the key in management of these fragility hip fracture patients during the COVID-19 pandemic [18] . It is recommended elderly patient with hip fractures should undergo minimal invasive procedure which requires less operating time, minimises blood loss, allows immediate post-operative weight-bearing to allow rehabilitation, and reduced length of stay with a primary aim to reduce exposure to coronavirus [18, 19] . Fragility hip fractures can be treated by Cemented bipolar hemi-replacement arthroplasties or Austin Moore prosthesis for intracapsular fractures and intra or extramedullary implants such as proximal femoral nail or locking dynamic hip screw intertrochanteric fractures. In addition, hemiarthroplasty can enable immediate mobilization and negate the risk of non-union in these cases. Intra-medullary nailing are load bearing and reduces the bone-implant interface. There is a higher mortality rate in patients with a hip fracture in elderly and an associated positive test for COVID-19. [38] .The patient with hip fractures and COVID-19-positive should be stabilized for respiratory parameters before surgery. The surgery in these cases will provide overall stability of the patient, seated mobilization, improvement in physiological ventilation, and general patient comfort in bed. [39] . Conservative treatment with traction with immobilization in bed can be considered for high risk COVID-19 patients with comorbidities. However, these bed-ridden patients' should be watched for deep venous thrombosis, urinary tract infections, and hospital-acquired pneumonia.

Absorbable sutures should be used for wound closure wherever possible, to avoid suture removal and a hospital visit [19] . During post-operative period and for rehabilitation, smartphone application and telemedicine facilities can be explored for consultation so that in person visits to the hospital can be avoided [33] .

Most osteoporotic vertebral fractures currently have little role for surgical intervention and these patients should be managed conservatively with immobilization using braces. Surgery should be reserved for exceptional cases with presence of neurological compromise.

Distal radius fracture, vertebral fracture without neurological deficit or proximal humerus fracture should be managed conservatively, as much as possible. The conservative treatment of an undisplaced vertebral fracture includes analgesic with period of bed rest and walking with a lumbar or thoracic-lumbar support. Fracture of distal radius if displaced should be reduced and maintain in removable splint or plaster of Paris slab. This allows self-removal of splints or plasters at home and avoids an out-patient visit. Similarly most of the fractures of the proximal humerus can be managed with an arm pouch sling. Follow up of these patients can be done through telemedicine facility whenever possible. Other than Plaster of Paris or resin casts, removable splints should be used for fracture management during this COVID-19 pandemic time to decrease the number of visits to healthcare facility. Some degree of mal-union may be accepted and this can be managed by reconstruction surgery in future period, if absolutely necessary [40, 41] .

COVID-19 has made us rethink how we manage fragility fractures. Prioritizing surgical treatment of obligatory fractures in patient care and conservative management of nonobligatory fractures will need ideas for the future including role of telemedicine.

Elimination of modifiable risk factors for osteoporosis (smoking, alcohol abuse) should also be considered during telemedicine.

Immobility is considered a moderate risk factor for osteoporosis. As people are remain in their homes due to lockdown this is also one of the challenge. Role of the physiotherapy should be properly explained to the patient to prevent fragility fractured. Patients should be prescribed to low or high impact aerobic activity (e.g., indoor walk more than 30 min a day), muscle-strengthening and balance exercises (use of weights for static exercises body exercise bikes).

A fall-prevention strategy for the elderly includes physical exercise, and education regarding risks within the home. The use of hip protector's orthosis can be recommended to patient's very high risk of fall [42] . Use of cane should also be explained to the patients to prevent fall. The factors that can be the source of falls such as physical barriers, wires, rugs, greasy floors, improper footwear, poor lighting and glare from the lamps, etc. must also be corrected. [43] Future directions

Recently researchers found that bisphosphonates have been used as new vaccine adjuvant eventually helps to shorten the race to COVID-19 immunity [44]. 

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