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Summary: In a population-based sample of British women aged over 70 years old, lean mass and peak lower limb muscle force were both independently associated with hip strength and fracture risk indices, thereby suggesting a potential benefit of promoting leg muscle strengthening exercise for the prevention of hip fractures in postmenopausal women.Introduction: To investigate cross-sectional associations of lean mass and physical performance, including lower limb muscle function, with hip strength, geometry and fracture risk indices (FRIs) in postmenopausal women.Methods: Data were from the Cohort of Skeletal Health in Bristol and Avon. Total hip (TH) and femoral neck (FN) bone mineral density (BMD), hip geometry and total body lean mass (TBLM) were assessed by dual x-ray absorptiometry (DXA). Finite element analysis of hip DXA was used to derive FN, intertrochanteric and subtrochanteric FRIs. Grip strength, gait speed and chair rise time were measured objectively. Lower limb peak muscle force and muscle power were assessed by jumping mechanography.Results: In total, 241 women were included (age = 76.4; SD = 2.6 years). After adjustment for age, height, weight/fat mass and comorbidities, TBLM was positively associated with hip BMD (βTH BMD = 0.36, P ≤ 0.001; βFN BMD = 0.26, P = 0.01) and cross-section moment of inertia (0.24, P ≤ 0.001) and inversely associated with FN FRI (− 0.21, P = 0.03) and intertrochanteric FRI (− 0.11, P = 0.05) (estimates represent SD difference in bone measures per SD difference in TBLM). Lower limb peak muscle force was positively associated with hip BMD (βTH BMD = 0.28, P ≤ 0.001; βFN BMD = 0.23, P = 0.008) and inversely associated with FN FRI (− 0.17, P = 0.04) and subtrochanteric FRI (− 0.18, P = 0.04). Associations of grip strength, gait speed, chair rise time and peak muscle power with hip parameters were close to the null.Conclusions: Lean mass and lower limb peak muscle force were associated with hip BMD and geometrical FRIs in postmenopausal women. Leg muscle strengthening exercises may therefore help prevent hip fractures in older women. [ABSTRACT FROM AUTHOR]

Summary: Previous work has shown that patients with vertebral fractures do less physical activity. However, the association between vertebral fracture and different components of physical activity is unclear. Our results suggest that vertebral fracture (VF) is associated with a reduction in activities involving bending, ambulation, and daily living, regardless of age. Introduction: The aim of this study was to determine whether osteoporotic VF is associated with reduced self-reported everyday routine physical activity and/or ability (PAA). Methods: A comprehensive search was undertaken using the databases of PubMed, Embase, Medline, Web of Science, and the 'grey' literature from 1950 to the end of July 2016. Standardised search terms for VF and PAAs were used. Four categories of PAA were included: (1) bending ability, (2) ambulatory activities, (3) reaching arms above shoulder level, and (4) activities of daily living (ADLs). Strict inclusion and exclusion criteria were used, and only studies that adjusted for age were included. For the meta-analysis, pooled OR and 95% confidence interval (CI) were calculated using a random-effects model. Results: Eleven studies in total were identified which had investigated the associations between the prevalent VF and the selected PAAs and expressed these as ORs or RR. Women (six studies) with VF had a 64% increase in difficulty forward bending compared to those without VF. Women (nine studies) with VF had a 27% increase in difficulty doing ambulatory activities, while no association was observed for men (four studies). Women also have 73% (five studies), 127% (three studies), and 100% (four studies) increase in difficulty reaching arms above shoulder, shopping, and preparing meals, respectively. Conclusion: Studies consistently show women with VF have reduced everyday activities, while much less research has been carried out in men. This information may be useful when designing interventions to improve physical function in people with osteoporotic VFs. [ABSTRACT FROM AUTHOR]

Objective Epidemiological studies have shown an association between increased bone mineral density (BMD) and osteoarthritis (OA), but whether this represents cause or effect remains unclear. In this study, we used a novel approach to investigate this question, determining whether individuals with High Bone Mass (HBM) have a higher prevalence of radiographic hip OA compared with controls. Design HBM cases came from the UK-based HBM study: HBM was defined by BMD Z-score. Unaffected relatives of index cases were recruited as family controls. Age-stratified random sampling was used to select further population controls from the Chingford and Hertfordshire cohort studies. Pelvic radiographs were pooled and assessed by a single observer blinded to case-control status. Analyses used logistic regression, adjusted for age, gender and body mass index (BMI). Results 530 HBM hips in 272 cases (mean age 62.9 years, 74% female) and 1702 control hips in 863 controls (mean age 64.8 years, 84% female) were analysed. The prevalence of radiographic OA, defined as Croft score ≥3, was higher in cases compared with controls (20.0% vs 13.6%), with adjusted odds ratio (OR) [95% CI] 1.52 [1.09, 2.11], P = 0.013. Osteophytes (OR 2.12 [1.61, 2.79], P < 0.001) and subchondral sclerosis (OR 2.78 [1.49, 5.18], P = 0.001) were more prevalent in cases. However, no difference in the prevalence of joint space narrowing (JSN) was seen (OR 0.97 [0.72, 1.33], P = 0.869). Conclusions An increased prevalence of radiographic hip OA and osteophytosis was observed in HBM cases compared with controls, in keeping with a positive association between HBM and OA and suggesting that OA in HBM has a hypertrophic phenotype. [ABSTRACT FROM AUTHOR]

The P2X[sub7] receptor is a member of the family of P2X purinergic receptors, which upon sustained activation forms large pores in the plasma membrane. In cells of hematopoietic origin, P2X[sub7] receptor activation has been shown to lead to multiple downstream events, including cytokine release, cell permeabilization, and apoptosis. This receptor has also been implicated in the generation of multinucleated giant cells, polykaryons, and osteoclasts. We have recently demonstrated that a blockade of this receptor inhibits osteoclast formation in vitro; therefore, we examined mice deficient in the P2X[sub7] receptor in the context of bone. These mice were healthy and displayed no overt skeletal problems. Furthermore, we were able to demonstrate their ability to form multinucleated cells, in particular osteoclasts, both in vivo and in vitro. We also demonstrate the ability of P2X[sub7]R[sup-/-] multinucleated osteoclasts, upon stimulation with maitotoxin (MTX), to form pores in the plasma membrane in vitro. These findings are consistent with the existence of an endogenous pore structure present in osteoclast precursor cells that can be activated either by the P2X[sub7] receptor, or in its absence, by alternative signals to mediate fusion and pore formation. These data provide further insight into the mode of action of the P2X[sub7] receptor. [ABSTRACT FROM AUTHOR]

Although animal studies suggest that there may be major differences between the effects of bisphosphonates and ovarian hormones on skeletal metabolism, whether this also holds for their actions in patients is unknown. To address this question, we compared the effects of 12 weeks treatment with HRT on bone turnover markers in osteopenic postmenopausal women with those of an amino-bisphosphonate. Women within 15 yr of the menopause, with a lumbar and/or femoral neck bone mineral density 1 S.D. below the predicted value, received either oestradiol valerate 2 mg and dydrogesterone 5 mg (E/D; n = 16) or aminohexane bisphosphonate 400 mg (AHBP; n =9). Urine and serum samples were collected on two separate occasions before starting treatment, and 1, 2, 4, 8 and 12 weeks afterwards. To assess bone resorption, we measured the urinary deoxypyridinoline/creatinine ratio (DPD/crea), while serum alkaline phosphatase (ALP), osteocalcin and C-terminal propeptide of type I collagen (CICP) were analysed to assess bone formation. Repeated measures analysis of variance revealed a highly significant decrease in DPD/crea over the treatment period. Furthermore, this pattern of response differed significantly between the two treatment groups, since DPD/crea was maximally suppressed within 2 weeks of starting AHBP, while E/D showed little decrease until 8 weeks. AHBP was also found to suppress ALP, osteocalcin and CICP more rapidly than E/D, the former reducing these markers by 8 weeks, while E/D caused little inhibition even by 12 weeks. We conclude that, in the doses used in this study, AHBP appears to suppress bone turnover significantly more rapidly than E/D, suggesting that clinically important differences may exist in the effects of bisghosphonates and ovarian hormones on bone metabolism. [ABSTRACT FROM PUBLISHER]

Although radiological studies suggest that Marfan syndrome is associated with osteopenia, investigations utilizing measurements of bone mass have yielded conflicting results. To address this question further, we measured bone mineral density (BMD) in 14 women with Marfan syndrome at the right hip and lumbar spine by dual energy X-ray absorptiometry (DXA). Results were compared with the age- and weight-matched reference population supplied by the DXA manufacturer, and with our own control population of normal women, the latter being matched for height, in addition to age and weight. We found that BMD was very similar in our Marfan women as compared with the two reference populations, at the lumbar spine and femoral neck, while trochanteric BMD was reduced. However, the relationship between an isolated reduction in trochanteric BMD and future fracture risk is unclear, and, on the basis of our results, we conclude that Marfan syndrome is not associated with a clinically significant increase in the risk of osteoporotic fracture. [ABSTRACT FROM PUBLISHER]