Secondary fracture rates and risk factors 1 year after a proximal femoral fracture under FLS.

INTRODUCTION: We aimed to investigate the secondary fracture rates and risk factors in patients with proximal femoral fractures using fracture liaison service (FLS) during the coronavirus disease (COVID)-19 pandemic. MATERIALS AND METHODS: In this multi-center prospective cohort study, patients with proximal femoral fractures who were treated surgically at three hospitals from April 2020 to March 2021 were included. Follow-up examinations at 6 and 12 months postoperatively were conducted to investigate the clinical data and ascertain whether osteoporosis treatment could be continued. RESULTS: A total of 316 patients with proximal femoral fractures were registered. During the follow-up period, 17 patients died and 67 patients could not visit the hospitals owing to the COVID-19 pandemic. In total, 172 patients who could be followed-up 12 months postoperatively were examined using dual-energy X-ray absorptiometry during hospitalization; underwent postoperative osteoporosis treatment, mainly with bisphosphonates (89.5%); and were administered medications continuously. Secondary fractures occurred within 1 year in 14 patients (8.1%). Multivariate analysis showed that patients who used sleeping pills and had a lower functional independence measure had an increased risk for developing secondary fractures. CONCLUSION: During the COVID-19 pandemic, secondary fractures can be prevented if the patients can be followed and osteoporosis treatment can be continued. Conversely, despite adequate osteoporosis drug examination and treatment, a certain number of secondary fractures still occurred. The finding that postoperative osteoporosis therapy using routine medications and rehabilitation is associated with secondary fractures may support the importance of establishing clinical standards consisting of a multidisciplinary collaboration for FLS.

The efficacy of teriparatide (Cinnopar®) on bone repair in mandibular fractures: A single blinded randomized clinical trial.

This study focused on the effects of teriparatide (CinnoPar) on healing and postoperative complications in mandibular bone fractures. In this single-blind randomized controlled trial, 30 patients with a mandibular fracture hospitalized for open reduction internal fixation were randomly assigned to the intervention (I) (n = 15) and control (C) (n = 15) groups. Both groups received daily acetaminophen and cephalexin for 1 week. For 1 month, Group I received daily subcutaneous teriparatide injections. The Radiographic Union Scale of the Mandible (RUSM) was used to assess mandibular bone fusion subjectively, and the Hounsfield unit (HU) was used to objectively assess radiodensity in a computed tomography (CT) scan. In both groups, the visual analog scale (VAS) score was used to assess postoperative complications such as pain, swelling, wound opening, pus secretion, and bitter taste. There was no significant difference in bone repair between the two groups in this study (P > 0.05). Teriparatide also had no effect on the postoperative complication rate in the control group (P > 0.05). Within the limitations of the study it seems that in mandibular fractures, teriparatide did not affect bone fusion or postoperative complications, so its use is not recommended for better bone fusion and fewer postoperative complications of mandibular fracture during the first month.

COVID-19 lockdown negatively impacted on adherence to denosumab therapy: incidence of non-traumatic fractures and role of telemedicine.

PURPOSE: Coronavirus disease (COVID-19) lockdowns have impacted on management of osteoporosis and the use of telemedicine is increasingly widespread albeit supported by little evidence so far. The aim of the study is to assess adherence to denosumab and incidence of non-traumatic fractures during the lockdown compared to the pre-COVID-19 year and to explore the effectiveness of telemedicine in the management of osteoporotic patients. METHODS: Retrospective, longitudinal, single-center study on patients receiving subcutaneous denosumab therapy every 6 months. Each patient was scheduled to undergo 2 visits: one during the pre-COVID-19 period (March 2019-March 2020) and another visit during the lockdown period (March 2020-March 2021). Data on new fractures, adherence, risk factors for osteoporosis and the modality of visit (telemedicine or face-to-face) were collected. RESULTS: The prevalence of non-adherent patients was higher during the lockdown (35 of 269 patients, 13.0%) than the pre-COVID-19 period (9 of 276 patients, 3.3%) (p < 0.0001). During the lockdown, the number of new non-traumatic fractures was higher than the pre-COVID-19 year (p < 0.0001): 10 patients out of 269 (3.7%) experienced a fragility fracture and 2 patients (0.7%) a probable rebound fracture during the lockdown period, whereas no patient had fragility/rebound fractures during the pre-COVID-19 period. No difference was found in the prevalence of non-adherence and new non-traumatic fractures comparing patients evaluated with tele-medicine to those evaluated with face-to-face visit. CONCLUSION: Non-adherent patients and new non-traumatic fractures (including rebound fractures) were more prevalent during the lockdown in comparison to the pre-COVID-19 period, regardless of the modality of medical evaluation.

Dispensing anti-osteoporotic drugs changed during the COVID-19 pandemic.

OBJECTIVES: Caring for osteoporosis patients has proven challenging during the COVID-19 pandemic due to repeated lockdowns in Austria. The distinct possibility of insufficient treatment regimens is therefore a matter of pressing concern. The aim of the study was to assess alterations in dispensing anti-osteoporotic drugs during the COVID-19 pandemic. PATIENTS/METHODS: This study was a nationwide retrospective register-based observational study which included all patients in Austria aged ≥50 who received at least one prescription for anti-osteoporotic medication between January 2016 and November 2020. Pseudonymised individual-level patients' data were obtained from social insurance authorities. Anti-osteoporotic agents were divided into: (i) oral bisphosphonates, (ii) intravenous bisphosphonates, (iii) selective estrogen receptor modulators (SERMs), (iv) teriparatide (TPTD) and (v) denosumab (DMAB). We used interrupted time series analysis with autoregressive integrated moving average models (ARIMA) to predict drug dispensing. RESULTS: There were 2,884,374 dispensations of anti-osteoporotic drugs to 224,598 patients between 2016 and 2020. The mean monthly prescriptions for oral bisphosphonates (-14.5 %) and SERMs (-12.9 %) decreased during the COVID-19 pandemic when compared to the non-COVID-19 period. Dispensing for intravenous bisphosphonates (1.7 %) and teriparatide (9.5 %) increased. Prescriptions for DMAB decreased during the first lock-down, however increased by 29.1 % for the total observation time. The Arima models showed that in March 2020 (beginning of the 1st COVID-19 lockdown), there was a decrease of 778 dispensings, with a further increase of 14 dispensings every month for denosumab; a decrease by 178 dispensings, with a further increase of 23 dispensings every month for zolendronic acid; a decrease by 2950 dispensings, but with a further increase of 236 dispensings every other month for ibandronate and a decrease by 1443 dispensing with a further decrease of 29 dispensings for alendronate than predicted, had the lockdown not occurred. CONCLUSIONS: The total number of prescriptions dispensed to patients treated with anti-osteoporotic medications declined rapidly during first COVID-19 lockdown. The observed decrease of DMAB during the first lockdown rebounded in the following months. Considering the massive treatment gap for osteoporosis, and the related fracture risk, clinicians should continue treatment, even during a pandemic.

Monthly Increase in Vitamin D Levels upon Supplementation with 2000 IU/Day in Healthy Volunteers: Result from "Integriamoci", a Pilot Pharmacokinetic Study.

Vitamin D (VD) is a calcium- and phosphate-controlling hormone used to treat bone disorders; yet, several other effects are progressively emerging. VD deficiency is highly prevalent worldwide, with suboptimal exposure to sunlight listed among the leading causes: oral supplementation with either cholecalciferol or calcitriol is used. However, there is a scarcity of clinical studies investigating how quickly VD concentrations can increase after supplementation. In this pilot study, the commercial supplement ImmuD3 (by Erboristeria Magentina®) was chosen as the source of VD and 2000 IU/day was administered for one month to 21 healthy volunteers that had not taken any other VD supplements in the previous 30 days. Plasma VD levels were measured through liquid chromatography coupled to tandem mass spectrometry after 7, 14, and 28 days of supplementation. We found that 95% of the participants had insufficient VD levels at baseline (<30 ng/mL; median 23.72 ng/mL; IQR 18.10-26.15), but after 28 days of supplementation, this percentage dropped to 62% (median 28.35 ng/mL; IQR 25.78-35.20). The median increase in VD level was 3.09 ng/mL (IQR 1.60-5.68) after 7 days and 8.85 ng/mL (IQR 2.85-13.97F) after 28 days. This study suggests the need for continuing VD supplementation and for measuring target level attainment.

Adherence to dosing schedule of denosumab therapy for osteoporosis during COVID-19 lockdown: an electronic medical record and pharmacy claims database study from Asia.

COVID-19 lockdowns have impacted management of chronic diseases such as osteoporosis. Adherence to the 6-monthly dosing schedule of denosumab, the parenteral anti-osteoporosis medication most often used in Singapore, was significantly reduced during the lockdown period compared to that during pre-COVID-19 times. Patients managed by endocrinologists were more likely to be adherent. PURPOSE: No study thus far has quantified actual adherence rates to anti-osteoporosis therapy with denosumab during COVID-19 or explored factors associated with it. We aimed to estimate the adherence rates to denosumab in Singaporean men and women during COVID-19 lockdown and to compare it with those during the pre-COVID-19 period. METHOD: We conducted this retrospective, electronic medical records, and pharmacy claims database study at Singapore General Hospital, the largest hospital in the country. Patients initiated on subcutaneous denosumab between August 2019 and December 2019 and were thus scheduled to receive the second dose during the COVID-19 first-wave period from February 2020 to June 2020 (lockdown group) were analyzed, as were patients initiated anytime on denosumab between September 2011 and December 2018 (pre-COVID-19 group). Data extracted from the hospital's electronic prescription platform and patients' pharmacy purchase records were matched. Adherence was defined as being punctual (with an allowable delay of up to 4 weeks) with the second dose scheduled 6 months from the 1st dose. A sensitivity analysis with an allowable delay up to 8 weeks was also performed. We compared the adherence rates between the two periods and explored factors associated with adherence. RESULTS: A total of 768 and 1458 patients respectively during the lockdown and pre-COVID-19 periods were analyzed. The mean adherence rate during lockdown was 63.9%. The odds of being adherent during lockdown were higher if patients were managed by endocrinologists as opposed to those by other specialists [OR 2.516 (95% CI: 1.836-3.448); p < 0.001]. Adherence rates during the pre-COVID-19 period was 75.4%. Overall, the odds of being adherent to denosumab was significantly lower during lockdown than that during the pre-COVID-19 period [OR 0.525 (95% CI 0.430-0.640); p < 0.001], and odds of being adherent were higher if patients were managed by endocrinologists than if they were managed by other specialists (OR 1.765 (95% CI: 1.444-2.158; p < 0.001). CONCLUSION: Adherence to denosumab was significantly lower during COVID-19 lockdown than the pre-COVID-19 period. The odds of being adherent were higher in patients managed by endocrinologists. Whether healthcare providers from certain specialties spend more time counselling and educating patients about the importance of adherence to osteoporosis medications needs to be explored further.

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

It is acknowledged that the COVID-19 pandemic has caused profound disruption to the delivery of healthcare services globally. This has affected the management of many long-term conditions including osteoporosis as resources are diverted to cover urgent care. Osteoporosis is a public health concern worldwide and treatment is required for the prevention of further bone loss, deterioration of skeletal micro-architecture, and fragility fractures. This review provides information on how the COVID-19 pandemic has impacted the diagnosis and management of osteoporosis. We also provide clinical recommendations on the adaptation of care pathways based on experience from five referral centres to ensure that patients with osteoporosis are still treated and to reduce the risk of fractures both for the individual patient and on a societal basis. We address the use of the FRAX tool for risk stratification and initiation of osteoporosis treatment and discuss the potential adaptations to treatment pathways in view of limitations on the availability of DXA. We focus on the issues surrounding initiation and maintenance of treatment for patients on parenteral therapies such as zoledronate, denosumab, teriparatide, and romosozumab during the pandemic. The design of these innovative care pathways for the management of patients with osteoporosis may also provide a platform for future improvement to osteoporosis services when routine clinical care resumes.

Changes in Menopausal Risk Factors in Early Postmenopausal Osteopenic Women After 13 Months of High-Intensity Exercise: The Randomized Controlled ACTLIFE-RCT.

The menopausal transition is a critical period in women's lives. Exercise might be the most promising non-pharmaceutic intervention to address the large variety of risk factors related to the pronounced estradiol decline during peri- and early-postmenopause. The aim of this study was to determine the effect of an 18-month multipurpose exercise program on risk factors and symptoms related to the menopausal transition. Fifty-four women 1-5 years postmenopause with osteopenia or osteoporosis were randomly assigned 1) to a high impact weight-bearing/high-intensity/velocity resistance training group (EG: n=27) exercising three times a week or 2) to an attendance control group (CG: n=27) that performed low-intensity exercise once a week. Both groups were supplemented with cholecalciferol and calcium. The primary study endpoint was bone mineral density (BMD) at lumbar spine (LS) and total hip, secondary outcomes were lean body mass (LBM), total and abdominal body percentage, metabolic syndrome Z-Score (MetS-Z), menopausal symptoms and muscle strength and power. Due to COVID-19, the study was stopped after 13 months. We observed significant effects for BMD-LS (EG: 0.002±.018 versus CG: -.009±0.018 mg/cm2, p=0.027) but not for BMD total hip (EG: -0.01±.016 versus CG: -.009±0.020 mg/cm2, p=0.129). LBM improved significantly in the EG and decreased in the CG (0.39±1.08 vs -0.37±1.34 kg, p=0.026). Total and abdominal body fat improved significantly in the EG and was maintained in the CG (-1.44±1.49 vs -0.02±1.55 kg, p=0.002 and -1.50±2.33 vs 0.08±2.07 kg, p=0.011). Significant effects in favor of the EG were also determined for menopausal symptoms (p=0.029), hip/leg extension strength (p<0.001) and power (p<0.001). However, changes of the MetS-Z did not differ significantly (p=0.149) between EG and CG. In summary, with minor exceptions, we demonstrated the effectiveness of a multipurpose exercise protocol dedicated to early-postmenopausal women on various risk factors and complaints related to the menopausal transition.

Influence of anti-osteoporosis treatments on the incidence of COVID-19 in patients with non-inflammatory rheumatic conditions.

Coronavirus disease 19 (COVID-19) is currently a global pandemic that affects patients with other pathologies. Here, we investigated the influence of treatments for osteoporosis and other non-inflammatory rheumatic conditions, such as osteoarthritis and fibromyalgia, on COVID-19 incidence. To this end, we conducted a cross-sectional study of 2,102 patients being treated at the Rheumatology Service of Hospital del Mar (Barcelona, Spain). In our cohort, COVID-19 cumulative incidence from March 1 to May 3, 2020 was compared to population estimates for the same city. We used Poisson regression models to determine the adjusted relative risk ratios for COVID-19 associated with different treatments and comorbidities. Denosumab, zoledronate and calcium were negatively associated with COVID-19 incidence. Some analgesics, particularly pregabalin and most of the studied antidepressants, were positively associated with COVID-19 incidence, whereas duloxetine presented a negative association. Oral bisphosphonates, vitamin D, thiazide diuretics, anti-hypertensive drugs and chronic non-steroidal anti-inflammatory drugs had no effect on COVID-19 incidence in the studied population. Our results provide novel evidence to support the maintenance of the main anti-osteoporosis treatments in COVID-19 patients, which may be of particular relevance to elderly patients affected by the SARS-CoV-2 pandemic.

[Gastrointestinal symptoms revealing COVID-19 in Malian breast cancer patient undergoing chemotherapy]. / Troubles digestifs révélateurs de la COVID-19 chez une patiente sous chimiothérapie pour cancer du sein au Mali.

In this review, we report a case of a bone's metastatic breast cancer in Malian patient treated by chemotherapy in whom SRAS-COV-2's diagnosis was made 9days after the onset gastrointestinal symptoms. Patient quickly died before any COVID-19's treatment. According to the poor outcomes of cancer patients with COVID-19, authors emphasize to an intensive attention to such patients in order to find the best therapeutic balance between the two pathologies during this pandemic.

"Effect of calcifediol treatment and best available therapy versus best available therapy on intensive care unit admission and mortality among patients hospitalized for COVID-19: A pilot randomized clinical study".

OBJECTIVE: The vitamin D endocrine system may have a variety of actions on cells and tissues involved in COVID-19 progression especially by decreasing the Acute Respiratory Distress Syndrome. Calcifediol can rapidly increase serum 25OHD concentration. We therefore evaluated the effect of calcifediol treatment, on Intensive Care Unit Admission and Mortality rate among Spanish patients hospitalized for COVID-19. DESIGN: Parallel pilot randomized open label, double-masked clinical trial. SETTING: University hospital setting (Reina Sofia University Hospital, Córdoba Spain.) PARTICIPANTS: 76 consecutive patients hospitalized with COVID-19 infection, clinical picture of acute respiratory infection, confirmed by a radiographic pattern of viral pneumonia and by a positive SARS-CoV-2 PCR with CURB65 severity scale (recommending hospital admission in case of total score > 1). PROCEDURES: All hospitalized patients received as best available therapy the same standard care, (per hospital protocol), of a combination of hydroxychloroquine (400 mg every 12 h on the first day, and 200 mg every 12 h for the following 5 days), azithromycin (500 mg orally for 5 days. Eligible patients were allocated at a 2 calcifediol:1 no calcifediol ratio through electronic randomization on the day of admission to take oral calcifediol (0.532 mg), or not. Patients in the calcifediol treatment group continued with oral calcifediol (0.266 mg) on day 3 and 7, and then weekly until discharge or ICU admission. Outcomes of effectiveness included rate of ICU admission and deaths. RESULTS: Of 50 patients treated with calcifediol, one required admission to the ICU (2%), while of 26 untreated patients, 13 required admission (50 %) p value X2 Fischer test p < 0.001. Univariate Risk Estimate Odds Ratio for ICU in patients with Calcifediol treatment versus without Calcifediol treatment: 0.02 (95 %CI 0.002-0.17). Multivariate Risk Estimate Odds Ratio for ICU in patients with Calcifediol treatment vs Without Calcifediol treatment ICU (adjusting by Hypertension and T2DM): 0.03 (95 %CI: 0.003-0.25). Of the patients treated with calcifediol, none died, and all were discharged, without complications. The 13 patients not treated with calcifediol, who were not admitted to the ICU, were discharged. Of the 13 patients admitted to the ICU, two died and the remaining 11 were discharged. CONCLUSION: Our pilot study demonstrated that administration of a high dose of Calcifediol or 25-hydroxyvitamin D, a main metabolite of vitamin D endocrine system, significantly reduced the need for ICU treatment of patients requiring hospitalization due to proven COVID-19. Calcifediol seems to be able to reduce severity of the disease, but larger trials with groups properly matched will be required to show a definitive answer.

Challenges of Treating a Patient With Advanced Prostate Cancer During the COVID-19 Pandemic.

A 78-year-old man had a medical history of hypertension, atrial fibrillation, chronic kidney disease, and metastatic castration-resistant prostate cancer (CRPC). He had progressed to first-line therapy for CRPC with abiraterone plus androgen-deprivation therapy (ADT) and as second-line therapy he was being treated with docetaxel, with biochemical progression in his last prostate specific antigen measurement. He was admitted to the hospital on April 2020, in the middle of the coronavirus disease 2019 (COVID-19) pandemic, because of painful bone lesions and deterioration of renal function.

The D-side of COVID-19: musculoskeletal benefits of vitamin D and beyond.

Coronavirus 2019 disease (COVID-19) mostly adversely affects the elderly, a population at higher risk for low serum 25-hydroxyvitamin D (25(OH)D) levels. In this viewpoint, we highlight the well-known musculoskeletal properties of vitamin D, which are particularly relevant in the context of COVID-19, suggesting further potential benefits through extra-skeletal effects. Maintaining optimal 25(OH)D is crucial to prevent falls, frailty and fractures in elderly patients, with low activity levels due to lockdown, or who are relatively immobilized during hospitalization and after discharge for prolonged periods of time. Hypovitaminosis D is also associated with susceptibility to respiratory infections, admissions to the intensive care unit, and mortality. We underscore the importance of achieving desirable serum 25(OH)D in COVID-19 elderly patients, to ensure beneficial musculoskeletal effects and possibly respiratory effects of vitamin D, in the context of COVID-19.

Standardized out-patient diagnosis and treatment process for osteoporosis clinics during the COVID-19 pandemic.

Since the end of 2019, China and other regions around the world have been facing a pandemic of novel coronavirus pneumonia (COVID-19). The virus is highly transmissible, and the human population is generally susceptible. Most patients with osteoporosis are postmenopausal women or elderly people with hypoimmunity, so the osteoporosis clinic has become a new hotspot for corona virus infection. During the COVID-19 pandemic, it is necessary to establish standardized out-patient protocols to provide safe and effective treatment for osteoporosis patients and medical staff. In an osteoporosis clinic, we advocate the following suggestions to prevent and control osteoporosis during the pandemic period: (1) specialized diagnosis and treatment techniques for osteoporosis patients in the outpatient care, including enhancing the prevention for outpatient medical staff, strengthening awareness of COVID-19 prevention, strictly screening outpatients with COVID-19 infection, and insistent administration of anti-osteoporosis drugs during outbreaks; (2) home prevention for osteoporosis patients including keeping windows open, exposing them to sunlight, supplementing them with enough protein, exercising regularly, and administrating calcium supplements; and (3) simplifying the follow-up and evaluation of osteoporosis using online platforms.

Osteoporosis Management in the Era of COVID-19.

Osteoporosis is a chronic condition that reflects reduced bone strength and an associated increased risk for fracture. As a chronic condition, osteoporosis generally requires sustained medical intervention(s) to limit the risks for additional bone loss, compromise of skeletal integrity, and fracture occurrence. Further complicating this issue is the fact that the abrupt cessation of some therapies can be associated with an increased risk for harm. It is in this context that the COVID-19 pandemic has brought unprecedented disruption to the provision of health care globally, including near universal requirements for social distancing. In this Perspective, we provide evidence, where available, regarding the general care of patients with osteoporosis in the COVID-19 era and provide clinical recommendations based primarily on expert opinion when data are absent. Particular emphasis is placed on the transition from parenteral osteoporosis therapies. It is hoped that these recommendations can be used to safely guide care for patients with osteoporosis until a return to routine clinical care standards is available. © 2020 American Society for Bone and Mineral Research.