Influence of Coaching on Effectiveness, Participation, and Safety of an Exercise Program for Postmenopausal Women with Osteoporosis: A Randomized Trial.

Purpose: We compared two different strategies providing professional coaching to administer an exercise program for women with postmenopausal osteoporosis (POP): individual training (IT) at home with trainer's supervision provided by telephone contacts at regular time-intervals or group training (GT) with trainer's live supervision. Our working hypothesis was that IT is a valid alternative to GT when GT is not feasible. Patients and Methods: This was a single-blind, randomized study. We recruited 52 women with POP, without significant comorbidity, and no participation in any structured exercise program within the previous 6 months. They were assigned randomly to IT or GT groups (n = 26 each). Distribution of age (IT: 68±4, GT: 67±8 years) and body mass index (IT: 23.0±2.5, GT: 21.4±5.1) was similar between groups. Each group performed the exercise program in two 1-hour sessions per week for 18 months. Primary outcome measure was Health-Related Quality of Life (HRQoL), as measured by the Short Osteoporosis Quality of Life Questionnaire. Secondary outcome measures focused on domains acknowledged to influence HRQoL (disability, fear of falling, weekly physical activity, physical function) or the effectiveness of the exercise program (retention, adherence, and safety). Significance level was set at p < 0.05. Results: No significant differences were observed between IT and GT groups for any domain. Retention, adherence, and safety were also similar. HRQoL, disability and fear of falling did not change between baseline and follow-up for either group. However, for both groups, physical function (knee flexion, shoulder mobility) and functional capacity (6-minute walking test) improved. Weekly physical activity levels increased from moderate range at baseline to intense at final assessment for both groups. Conclusion: IT and GT supervised exercise programs for women with POP provide similar effectiveness, participation and safety. Hence, both modalities should be considered for future translation in clinical practice of exercise recommendations for POP.

Discontinuing Denosumab: Can It Be Done Safely? A Review of the Literature.

Denosumab, which has been approved for the treatment of osteoporosis since 2010, is a fully humanised monoclonal antibody against a cytokine, receptor activator of nuclear factor kappa B ligand (RANKL), involved in bone resorption. Continued use of denosumab results in a potent and sustained decrease in bone turnover, an increase in bone mineral density (BMD), and a reduction in vertebral and hip fractures. The anti-resorptive effects of denosumab are reversible upon cessation, and this reversal is accompanied by a transient marked increase in bone turnover that is associated with bone loss, and of concern, an increased risk of multiple vertebral fractures. In this review, we outline the effects of denosumab withdrawal on bone turnover markers, BMD, histomorphometry, and fracture risk. We provide an update on recent clinical trials that sought to answer how clinicians can transition away from denosumab safely with follow-on therapy to mitigate bone loss and summarise the recommendations of various international guidelines.

SARS-Cov-2 Infection in Postmenopausal Women. New Data on Menopause Hormone Therapy (preprint)

Objective: To address the factors involved in hospital admission and medical follow up in postmenopausal women with COVID-19 diagnosis. Methods: Retrospective observational study. Postmenopausal women aged between 40-70 years since September 2020 until June 2021 with COVID-19 diagnosis were included. Of the 300 women cohort, 50 were receiving menopause hormone therapy (MHT) Results: 288 patients were analyzed. The mean age was 56.20 years (+/-6.06y SD). Age (p=0.030), High blood pressure (HBP) (p=0.002), respiratory disorders (p=0.003), depression (p=0.028) and fibromyalgia (p=0.030) were associated with a greater risk for hospital admission, while MHT was found as a protective factor (p=0.042). Being a health professional (p<0.001), HBP (p=0.029), respiratory disorders (p=0.022), vitamin D deficiency (p=0.010), depression (p=0.005) and fibromyalgia (p=0.001) were related with a longer follow up while MHT was related with a shorter one (p=0.010). Regression analysis showed that HBP and respiratory disorders acted as independent factors for hospital admission while MHT and fibromyalgia were for the length of follow up. Conclusions: MHT has a positive impact in postmenopausal women with SARS-CoV-2 infection. HBP and respiratory disorders are associated with a higher risk of hospital admission of these patients.

Menopausal osteoporosis: screening, prevention and treatment.

Screening for osteoporosis in women can be based on age and weight, using the Osteoporosis Screening Tool for Asians and assessment for other risk factors such as early menopause, Chinese ethnicity and other secondary factors. Based on the resulting risk profile, women can be triaged to dual-energy X-ray absorptiometry (DEXA) scanning for definite diagnosis of osteoporosis. Treatment should be considered in women with previous fragility fractures, DEXA-diagnosed osteoporosis and high risk of fracture. Exercise improves muscle function, can help prevent falls and has moderate effects on improvements in bone mass. Women should ensure adequate calcium intake and vitamin D. Menopausal hormone therapy (MHT) effectively prevents osteoporosis and fractures, and should be encouraged in those aged < 50 years. For women aged < 60 years, MHT or tibolone can be considered, especially if they have vasomotor or genitourinary symptoms. Risedronate or bisphosphonates may then be reserved for those aged over 60 years.

Detraining Effects on Musculoskeletal Parameters in Early Postmenopausal Osteopenic Women: 3-Month Follow-Up of the Randomized Controlled ACTLIFE Study.

Periods of absence from supervised group exercise while maintaining physical activity might be a frequent pattern in adults' exercise habits. The aim of the present study was to determine detraining effects on musculoskeletal outcomes after a 3-month detraining period in early post-menopausal, osteopenic women. Due to the COVID-19 pandemic, we terminated the 18-month randomized controlled ACTLIFE exercise intervention immediately after the 13-month follow-up assessment. This put an abrupt stop to the high-intensity aerobic and resistance group exercise sessions undertaken three times per week by the exercise group (EG: n = 27) and the gentle exercise program performed once per week for the attention control group (CG: n = 27); but both groups were permitted to conduct individual outdoor activity for the 3-month lock-down period. Study endpoints were lean body mass (LBM), bone mineral density (BMD) at the lumbar spine (LS), maximum hip-/leg extension strength and power. Detraining-induced reductions of LBM, hip/leg strength and power (but not BMD-LS) were significantly greater (p < 0.001 to p = 0.044) compared with the CG. Significant exercise effects, i.e. differences between EG and CG, present after 13 months of exercise, were lost after 3 months of detraining for LBM (p = 0.157) and BMD-LS (p = 0.065), but not for strength (p < 0.001) and power (p < 0.001). Of note, self-reported individual outdoor activities and exercise increased by about 40% in both groups during the lock-down period. Three months' absence from a supervised group exercise protocol resulted in considerable detraining effects for musculoskeletal parameters. Thus, exercise programs for adults should be continuous rather than intermittent.Trial registration number: ClinicalTrials.gov: NCT04420806, 06.05.2020.

Effects of COVID-19 Lockdown on Adherence to Individual Home- or Gym-Based Exercise Training among Women with Postmenopausal Osteoporosis.

Adherence is important for an exercise program's efficacy. This study aims at investigating whether the COVID-19 lockdown had different consequences on the adherence to an exercise program specifically designed for women with postmenopausal osteoporosis when administered as individual home training (IHT) or gym group training (GGT). At the start of the lockdown, which imposed the temporary closure of any gym activities, GGT participants were invited to continue to exercise at home. IHT participants continued to exercise at home as usual. Adherence was recorded via logs and measured as the percentage of exercise sessions actually performed out of the total number of scheduled sessions in three 1-month periods: one before (PRE) and two after (M1 and M2) the beginning of lockdown. Before lockdown, IHT (66.8% ± 26.6) and GGT (76.3% ± 26.6) adherence were similar. During lockdown, IHT participation increased (M1: 81.5% ± 31.0; M2: 88.0% ± 28.3), while that of GGT showed no statistical differences (M1: 79.4% ± 34.2; M2: 80.6% ± 36.4). Exercise protocols based on supervised gym practice must consider the possibility of disruptive events, which could cause a sudden interruption of gym activity and include educational initiatives to instruct participants to exercise effectively and safely without a trainer's direct supervision.

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.

Raloxifene as a treatment option for viral infections.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused corona virus disease 2019 (COVID-19) pandemic and led to mass casualty. Even though much effort has been put into development of vaccine and treatment methods to combat COVID-19, no safe and efficient cure has been discovered. Drug repurposing or drug repositioning which is a process of investigating pre-existing drug candidates for novel applications outside their original medical indication can speed up the drug development process. Raloxifene is a selective estrogen receptor modulator (SERM) that has been approved by FDA in 1997 for treatment and prevention of postmenopausal osteoporosis and cancer. Recently, raloxifene demonstrates efficacy in treating viral infections by Ebola, influenza A, and hepatitis C viruses and shows potential for drug repurposing for the treatment of SARS-CoV-2 infection. This review will provide an overview of raloxifene's mechanism of action as a SERM and present proposed mechanisms of action in treatment of viral infections.