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.

Spine Fragility Fracture Prediction Using TBS and BMD in Postmenopausal Women: A Bayesian Approach.

The trabecular bone score (TBS) estimates bone microarchitecture and can be used to evaluate the risk of osteoporotic fractures independently of bone mineral density (BMD). In this retrospective case-control study, we tested and compared the ability of TBS and lumbar spine BMD (LS-BMD) to predict vertebral fragility fractures. The inclusion criteria were female sex, age range 50-90 years, menopause, and clinical risk factors for osteoporosis. Patients with secondary osteoporosis were excluded. LS-BMD and TBS were measured at the L1-L4 vertebral level. The ability of the two diagnostic systems in predicting vertebral fragility fractures was assessed by combining LS-BMD and TBS according to the Bayesian "OR rule" (the diagnosis is negative only for those negative for both tests, and it is positive for those who were positive for at least one test) or to the "AND rule" (the diagnosis is positive only for those positive to both tests and is negative for those negative for at least one test). Of the 992 postmenopausal women included, 86 had a documented vertebral fragility fracture. At the cutoff value used in the present study, the TBS and LS-BMD showed a similar diagnostic ability to predict vertebral fragility fractures, having positive predictive values (PPV) of, respectively, 13.19% and 13.24%. Negative predictive values (NPV) were, respectively, 95.40% and 94.95%. Compared to that of each single diagnostic system, the "OR-rule" significantly increased the NPV to 97.89%, while no statistically significant differences were found by using the "AND-rule". In conclusion, the present study highlights the possibility that combining LS-BMD and TBS could improve their predictive ability in diagnosing vertebral fragility fractures, and that there is a significant probability of absence of fractures in women who test negative to both diagnostic systems.

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.

Levels and Factors Associated with Resilience in Italian Healthcare Professionals during the COVID-19 Pandemic: A Web-Based Survey.

BACKGROUND: Resilience is defined as the capacity to cope successfully with change or adversity. The aims of our study were to investigate levels of resilience in Italian healthcare professionals (HCPs) during the Coronavirus disease 2019 (COVID-19) pandemic and to identify potential predictors of resilience. METHODS: We performed a web-based survey of HCPs (n = 1009) working in Italian hospitals during the COVID-19 pandemic. The survey contained a 14-item resilience scale (RS14) and questionnaires to evaluate depression and anxiety symptoms. Non-HCP individuals (n = 375) from the general population were used for comparison. RESULTS: HCPs showed significantly lower resilience compared to the control group (p = 0.001). No significant differences were observed after stratification for geographical area, work setting, role, or suspected/confirmed diagnosis of COVID-19. In a linear regression analysis, RS14 was inversely correlated with depression (R2 = 0.227, p < 0.001) and anxiety (R2 = 0.117, p < 0.001) and directly correlated with age (R2 = 0.012, p < 0.001) but not with body mass index (BMI, R2 = 0.002, p = 0.213). In male HCPs, higher depression score (odds ratio (OR) 1.147, p < 0.001) or BMI (OR 1.136, p = 0.011) significantly predicted having low resilience. In female HCPs, higher depression score (OR 1.111, p < 0.0001) and working in a COVID-19 free setting (OR 2.308, p = 0.002) significantly predicted having low resilience. HCPs satisfied with personal protective equipment had higher levels of resilience (p < 0.010). CONCLUSIONS: Our findings suggest that resilience was lower in Italian HCPs than in the general population after the first COVID-19 wave. Specific factors can be identified, and targeted interventions may have an important role to foster resilience of HCPs.

A Randomized Clinical Trial to Evaluate the Efficacy and Safety of the ACTLIFE Exercise Program for Women with Post-menopausal Osteoporosis: Study Protocol.

Osteoporosis (OP) is a systemic disease of the skeleton characterized by increased risk of fracture. There is a general consensus on the efficacy of physical activity in the prevention of bone loss, falls and fractures, but there is no agreement on the best setting to exercise. The aim of the study is to evaluate the efficacy of a 12-months exercise protocol for women with post-menopausal OP when administered as individual home training (IHT) versus gym group training (GGT). The study is a randomized trial with two parallel groups. Sedentary patients with primary post-menopausal osteoporosis are recruited at the Istituto Ortopedico Rizzoli of Bologna. In the first group, the 12-month ACTLIFE program is performed as IHT, while in the second as GGT. The program is aimed at improving joint mobility, muscle force, balance, motor coordination and endurance. The study is single blinded. Patients are assessed at baseline and after 6 and 12 months. The primary outcome is the modification of quality of life measured with the Short Osteoporosis Quality of Life Questionnaire (ECOS-16). The findings of this study will highlight advantages and disadvantages of exercising in the two different settings and provide evidence on how to increase physical activity in osteoporotic women.

Potassium Citrate Supplementation Decreases the Biochemical Markers of Bone Loss in a Group of Osteopenic Women: The Results of a Randomized, Double-Blind, Placebo-Controlled Pilot Study.

The relationship involving acid-base imbalance, mineral metabolism and bone health status has previously been reported but the efficacy of the alkalizing supplementation in targeting acid overload and preventing bone loss has not yet been fully elucidated. In this randomized, double-blind, placebo-controlled study, the hypothesis that potassium citrate (K citrate) modifies bone turnover in women with postmenopausal osteopenia was tested. Three hundred and ten women were screened; 40 women met the inclusion criteria and were randomly assigned to the treatment or the placebo group. They were treated with K citrate (30 mEq day-1) or a placebo in addition to calcium carbonate (500 mg day-1) and vitamin D (400 IU day-1). At baseline and time points of 3 and 6 months, serum indicators of renal function, electrolytes, calciotropic hormones, serum bone turnover markers (BTMs), tartrate-resistant acid phosphatase 5b (TRACP5b), carboxy-terminal telopeptide of type I collagen (CTX), bone alkaline phosphatase (BAP), procollagen type 1 N terminal propeptide (PINP)), and urine pH, electrolytes, and citrate were measured. The follow-up was completed by 17/20 patients in the "K citrate" group and 18/20 patients in the "placebo" group. At baseline, 90% of the patients exhibited low potassium excretion in 24 h urine samples, and 85% of cases had at least one urine parameter associated with low-grade acidosis (low pH, low citrate excretion). After treatment, CTX and BAP decreased significantly in both groups, but subjects with evidence of low-grade acidosis gained significant benefits from the treatment compared to the placebo. In patients with low 24h-citrate excretion at baseline, a 30% mean decrease in BAP and CTX was observed at 6 months. A significant reduction was also evident when low citrate (BAP: -25%; CTX: -35%) and a low pH (BAP: -25%; CTX: -30%) were found in fasting-morning urine. In conclusion, our results suggested that K citrate supplementation improved the beneficial effects of calcium and vitamin D in osteopenic women with a documented potassium and citrate deficit, and a metabolic profile consistent with low-grade acidosis.

The Trabecular Bone Score Predicts Spine Fragility Fractures in Postmenopausal Caucasian Women Without Osteoporosis Independently of Bone Mineral Density.

INTRODUCTION: The trabecular bone score (TBS) is a gray-level textural metric that can be extracted from the two-dimensional lumbar spine dual-energy X-ray absorptiometry (DXA) image. TBS is related to bone microarchitecture. Several literature data suggest that TBS predicts fracture risk as well as lumbar spine bone mineral density (LS-BMD) measurements in postmenopausal women. OBJECTIVE: A retrospective case-control study assessing the ability of the TBS to predict spine fragility fractures (SFF) in postmenopausal women with or without osteoporosis (diagnosed by T-score≤-2.5). METHODS: LS-BMD and the TBS were determined in the L1-L4 vertebrae. Statistical analyses were carried out in the entire group of women (entire-group) (n.699), in women both with osteoporosis (osteoporosis-subgroup) (n.253) and those without osteoporosis (non-osteoporosis-subgroup) (n. 446). RESULTS: At the unpaired t-test, both the TBS and the LS-BMD (p≤0.001) were lower in women with SFF (n.62) in the entire-group. In the non-osteoporosis subgroup, the TBS (p≤0.009) was lower in women with SFF (n.29). In the osteoporosis subgroup, the LS-BMD (p≤0.003) was lower in women with SFF (n.33). Considering the TBS and LS-BMD separately in a block logistic regression, the TBS was associated with SFF in the entire-group (odds ratio (OR): 1.599, 95% confidence interval (CI): 1.021-2.128) and in the non-osteoporosis-subgroup (OR: 1.725, 95% CI:1.118-2.660) whereas LS-BMD was associated with SFF in the entire-group (OR: 1.611, 95% CI: 1.187-2.187) and in the osteoporosis-subgroup (OR: 2.383, 95% CI: 1.135-5.003). According to forward logistic regression, entering the TBS, LS-BMD and confounders as predictors, the LS-BMD in the entire-group (OR: 1.620, 95% CI: 1.229-2.135) and in the osteoporosis subgroup (OR: 2.344, 95% CI: 1.194-4.600), and the TBS in the non-osteoporosis subgroup (OR: 1.685, 95% CI: 1.131-2.511) were the only predictors of SFFs. CONCLUSIONS: In the entire-group, the TBS predicted SFFs almost as well as LS-BMD, but not independently of it. The TBS, but not LS-BMD, predicted SFFs in the non-osteoporosis subgroup.

Autophagy activation in COL6 myopathic patients by a low-protein-diet pilot trial.

A pilot clinical trial based on nutritional modulation was designed to assess the efficacy of a one-year low-protein diet in activating autophagy in skeletal muscle of patients affected by COL6/collagen VI-related myopathies. Ullrich congenital muscular dystrophy and Bethlem myopathy are rare inherited muscle disorders caused by mutations of COL6 genes and for which no cure is yet available. Studies in col6 null mice revealed that myofiber degeneration involves autophagy defects and that forced activation of autophagy results in the amelioration of muscle pathology. Seven adult patients affected by COL6 myopathies underwent a controlled low-protein diet for 12 mo and we evaluated the presence of autophagosomes and the mRNA and protein levels for BECN1/Beclin 1 and MAP1LC3B/LC3B in muscle biopsies and blood leukocytes. Safety measures were assessed, including muscle strength, motor and respiratory function, and metabolic parameters. After one y of low-protein diet, autophagic markers were increased in skeletal muscle and blood leukocytes of patients. The treatment was safe as shown by preservation of lean:fat percentage of body composition, muscle strength and function. Moreover, the decreased incidence of myofiber apoptosis indicated benefits in muscle homeostasis, and the metabolic changes pointed at improved mitochondrial function. These data provide evidence that a low-protein diet is able to activate autophagy and is safe and tolerable in patients with COL6 myopathies, pointing at autophagy activation as a potential target for therapeutic applications. In addition, our findings indicate that blood leukocytes are a promising noninvasive tool for monitoring autophagy activation in patients.

Body composition, muscle strength, and physical function of patients with Bethlem myopathy and Ullrich congenital muscular dystrophy.

OBJECTIVE: To determine the contributions of body mass, adiposity, and muscularity to physical function and muscle strength in adult patients with Bethlem myopathy (BM) and Ullrich congenital muscular dystrophy (UCMD). MATERIALS AND METHODS: Evaluation involved one UCMD and 7 BM patients. Body composition was determined by body mass index (BMI) and dual-energy-X-ray-absorptiometry (DXA), muscle strength by dynamometry, physical function by the distance walked in 6 minutes (6MWD), forced vital capacity (FVC) by a spirometer. RESULTS: Six participants were of normal weight and 2 overweight based on BMI; all were sarcopenic based on appendicular fat free mass index (AFFMI); and 7 were sarcopenic obese based on AFFMI and % fat mass. Average muscle strength was reduced below 50% of normal. The 6MWD was in BM patients 30% less than normal. FVC was reduced in 4 of the BM patients. Muscle strength had a good correlation with the physical function variables. Correlation between muscle strength and BMI was poor; it was very high with AFFMI. AFFMI was the best single explicator of muscle strength and physical function. CONCLUSION: Muscle mass determined by DXA explains most of the variability of the measures of muscle strength and physical function in patients with BM and UCMD.

Quantitative ultrasound at the phalanxes discriminates osteoporotic women with vertebral but not with hip fracture.

Caucasian postmenopausal women with vertebral fracture (38), hip fracture (38) and without fracture (124) were measured by spine and femoral neck bone mineral density (BMD) (Norland XR 36), and two quantitative ultrasound (US) or QUS parameters (Igea DBM sonic 1200): the amplitude-dependent speed of sound (Ad-Sos) and the US bone profile score (UBPS), at the proximal hand phalanxes to investigate the ability of QUS to detect previous fracture. Age, height and weight were not different among groups, but menopausal age was lower with vertebral fracture (p < 0.005). QUS parameters of hip (AdSos = 1806.2 +/- 104.6 m s(-1); UBPS = 0.22 +/- 0.13) or spine fracture (AdSos = 1774.4 +/- 90.0 m s(-1); UBPS = 0.19 +/- 0.10) were not significantly lower than controls (AdSos = 1819.1 +/- 111.9 m s(-1); UBPS = 0.25 +/- 0.17), and BMD of hip (spine: 756.0 +/- 138.9 mg cm(-2); femoral neck: 583.6 +/- 61.8 mg cm(-2)) and vertebral (spine: 727.4 +/- 120.4 mg cm(-2); femoral neck: 592.8 +/- 82.1 mg cm(-2);) fracture was lower than controls (spine: 829.2 +/- 167.6 mg cm(-2); femoral neck 665.0 +/- 108.9 mg cm(-2)) (p < 0.001). Spine and femoral neck BMD significantly separated both types of fractures from controls, but AdSos and UBPS significantly separated only vertebral fractures. Femoral neck BMD has the best receiver operating characteristic (ROC) area for both hip (0.715, SE 0.043) and vertebral (0.693, SE 0.047) fractures, being significantly better (p < 0.01) than that of AdSos (0.503, SE 0.056) and UBPS (0.501, SE 0.057) for hip fractures, but not for vertebral fractures (AdSos 0.604, SE 0.050; UBPS 0.563, SE 0.048). In conclusion, QUS at hand phalanxes predicts vertebral fracture as effectively as BMD, but does not predict hip fracture.