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Purpose: The menopausal transition is a critical period in wo-men’s lives. The central aim of the present study was to evaluate the effect of a multimodal exercise protocol on the cardiometa-bolic risk factor potentially related to menopausal transition in early postmenopausal women. Methods: Fifty-four (54) early-postmenopausal women (54.0±1.8 years) were randomly assigned to two groups: (1) exercise group (EG: n=27) which conducted a high intensity aerobic and resistance training three times/week and (2) active control group (CG: n=27) exercising once a week with low exercise inten-sity. Besides bone density, the main variable of this project, the outcome variable in this thesis was also cardiometabolic risk, as summarized by the Metabolic Syndrome (MetS) Z-Score. We applied Intention-to-Treat (ITT) and Per Protocol Analyses (PPA) with multiple imputation and used standardized mean differences to illustrate the effects. Results: After 16 weeks of exercise two participants (EG: n=1; CG: n=1) were lost to follow-up. Effects for the MetS Z-Score were moderate (EG:-0.36±1.36 vs. CG: 0.51±2.28; SMD: 0.47, 95% CI:-0.08 to 1.03), albeit borderline non-significant (ITT: p=.089; PPA: p=.060). Conclusion: The present multimodal exercise protocol just fai-led to affect the MetS Z-Score and its underlying cardiometabolic risk factors. Whether this result can be generalized to the entire cohort of early-postmenopausal women or whether it has to be attributed to the only moderately high exercise intensity during the early weeks of the intervention along with a relatively short intervention period remains to be evaluated.

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.

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&minus, 1) or a placebo in addition to calcium carbonate (500 mg day&minus, 1) and vitamin D (400 IU day&minus, 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 &ldquo, K citrate&rdquo, group and 18/20 patients in the &ldquo, placebo&rdquo, 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: &minus, 25%, CTX: &minus, 35%) and a low pH (BAP: &minus, 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.

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.

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.

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.

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 (p0.005). 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)) (p0.001). 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 (p0.01) 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.

Low bone mineral density (BMD) and, probably, the rate of bone loss (RBL) are associated with the risk of osteoporotic fractures. To estimate the risk of nonspinal fracture in osteoporotic women, we measured BMD and RBL in a prospective study (average follow-up, 5.38 years) in 656 postmenopausal women. The women were considered in three groups: group A (whole population), group B (women under the age of 65 years) and group C (women over the age of 65 years). At the beginning of the study, BMD was measured at the distal radius (DR) and at the proximal radius (PR) using a single-energy densitometer. BMD measurements made 2 years previously in the same patients were used to calculate RBL. Then patients were checked annually for nonspine fracture due to minor trauma. During follow-up, 121 nonspinal fractures were detected. Women with fractures were older and had lower BMD. With the Cox regression, age-corrected BMD at both DR and PR predicts fracture risk in groups A and B but not in group C. After correction for potential confounders, DR still predicts fractures in groups A and B whereas PR predicts fractures only in group B. In group C, only the RBL at the PR was predictive of the fracture risk as well as in the other two groups. Specific types of fractures are predictable in the whole population at the wrist. In conclusion, radial BMD predicts the risk of nonspine fractures except in women over the age of 65 years. The RBL at the PR is an effective predictor of fracture risk also in women over the age of 65 years.

It is proven that, from a technical point of view, ultrasound transmission velocity (UTV) measurement can easily be taken at the distal end of the radius. The reproducibility of UTV is good (coefficient of variation 0.3% intraoperator and 0.5% interoperator). 248 normal and 65 osteoporotic women were then studied to establish the range of UTV values and to compare the ability of UTV and bone mineral density (BMD) measurement, taken at the same skeletal sites, to detect osteoporotic fragility. Osteoporosis was defined by the presence of atraumatic vertebral fractures on an X-ray of the spine. Ultrasound velocity averaged 1570.5 +/- 43.3 m s-1 in normal and 1519.2 +/- 15.2 m s-1 in osteoporotic women; the difference is also statistically significant (p < 0.01) for BMD. Both BMD and UTV decline after menopause and are significantly correlated with age. A weak correlation (r = 0.68) was found between UTV and BMD; this supports the thesis that ultrasound velocity measures bone mass as well as other fragility components of bone distinct from the decrease of mass. Receiver operating characteristic (ROC) curve analysis showed that UTV discriminates between normal and osteoporotic patients at least as well as radial BMD, indicating that UTV is a new available diagnostic modality which can be used to screen osteoporotic subjects.