Bone Reports最新文献

Objectives

Methods

Results

Conclusion

Background

Methods

Results

Conclusion

Background

Vitamin D is vital for musculoskeletal health, and supplementation may lower risk of falls. Past research in residential aged care (RAC) settings on the effects of vitamin D on falls have reported inconclusive findings, partly due to study design limitations. We utilised a longitudinal study design to assess the association between the use of vitamin D and falls over 36 months in RAC.

Method

A longitudinal cohort study was conducted using routinely collected electronic data spanning 9 years from 27 RAC facilities in Sydney, New South Wales, Australia. The study included 4520 permanent residents aged 65 years or older who were admitted for the first time from 1 July 2014 and stayed for a minimum of one month. We identified daily vitamin D usage over 36 months, and measured adherence using the Proportion of Days Covered (PDC) metric. A PDC value of ≥80 % signifies optimal adherence. Primary outcomes were the number of all falls and injurious falls. A rolling time-varying predictor-outcome approach and Generalized Estimating Equations (GEE) were applied to determine the longitudinal link between vitamin D supplement use and subsequent risk of falls.

Results

Over two-thirds of residents (67.8 %; n = 3063) received vitamin D supplements during their stay, with a median PDC of 74.8 % among users, and 44.6 % (n = 1365) achieving optimal adherence. Increasing age, osteoporosis or fracture history, and dementia were associated with a greater likelihood of achieving optimal adherence. Crude fall incident rates were 8.05 and 2.92 incidents per 1000 resident days for all falls and injurious falls respectively. After accounting for relevant demographic and clinical factors, no significant links were observed between vitamin D supplement usage and fall outcomes: all falls (Incident Rate Ratio [IRR] 1.01; 95 % CI 1.00–1.02; P = 0.237) and injurious falls (IRR 1.01; 95 % CI 1.00–1.02; P = 0.091).

Conclusion

Vitamin D supplementation was not associated with a reduced risk of falls, suggesting it is not an effective intervention for preventing falls in RAC. While clinicians should ensure adequate vitamin D intake for residents' nutritional and bone health, it should not be a standalone falls prevention intervention in RAC populations.

Introduction

Bone mineral density (BMD) is reduced in patients with human immunodeficiency virus (HIV) infection. Trabecular bone score (TBS) is an additional feature calculated by dual-energy X ray absorption (DXA) that measures texture inhomogeneity at lumbar spine level, providing an index of bone microarchitecture. However, its clinical value still needs to be fully addressed. Aims of the study were to assess BMD and TBS in a cohort of patients with HIV compared to a population of healthy subjects and to investigate the prognostic value of TBS in HIV infected patients.

Method

Bone health was assessed by DXA in 165 patients with HIV infection (120 men, mean age 40 ± 7 years) and in 164 healthy subjects (53 male, mean age 37 ± 10 years). BMD was measured at level of lumbar spine (L1-L4), femoral neck and total hip. TBS was computed from the images of lumbar spine using machine proprietary software.

Results

BMD at femoral neck level was similar in HIV infected patients and healthy subjects (p = 0.57), whereas BMD measured in total femur was lower in HIV infected patients compared to healthy subjects (p < 0.05). Although mean BMD in lumbar spine was similar between HIV infected patients and healthy subjects (p = 0.90), mean lumbar TBS was lower in patients with HIV infection compared to healthy subjects (p < 0.05). Age, sex and HIV infection resulted independent predictors of reduced TBS. In HIV infected patients age, sex and protease inhibitor duration resulted independent predictors of reduced TBS. TBS was a significant predictor of vertebral fractures during follow-up (p < 0.05).

Conclusion

Patients with HIV infection have a significant reduction of TBS, a texture parameter related to bone microarchitecture that may provide skeletal information that is not captured from the standard BMD measurement.

Excessive production of Transforming Growth Factor β (TGFβ) is commonly associated with dominant and recessive forms of OI. Previous reports have indicated that administration of TGFβ-targeted antibodies maybe of potential therapeutic benefit to OI patients. However, direct targeting of TGFβ is likely to cause multiple adverse effects including simulation of autoimmunity. In the current study we use patient-derived normal and OI fibroblasts, osteoblasts and OIM mouse models to determine the effects of Losartan, an angiotensin II receptor type 1 (AT1) antagonist, on TGFβ signalling and bone morphology in OI. In OIM mice bred on a mixed background administration of 0.6 g/L losartan for 4 weeks was associated with a significant reduction in TGFβ from 79.2 g/L in the control to 60.0 ng/ml following losartan (p < 0.05), reduced osteoclast activity as measured by CTX from 275.9 ng/ml in the control to 157.2 ng/ml following 0.6 g/L of losartan (p < 0.05) and increased cortical bone thickness (P < 0.001). Furthermore in OIM mice bred on a C57BL/6 background 0.6 g/L losartan increased trabecular bone volume in the tibiae (P < 0.05) and the vertebrae (P < 0.01), increased cortical bone thickness (P < 0.001) reduced the trabecular pattern factor (P < 0.01 and P < 0.001 for the tibiae and vertebrae respectively), reduced osteoclast (P < 0.05) and osteoblast (P < 0.01) numbers as well as reducing the area of bone covered by these cell types. Interestingly, losartan did not affect immune cells infiltrating into bone, nor did this drug alter TGFβ signalling in normal or OI fibroblasts. Instead, losartan reduced SMAD2 phosphorylation in osteoblasts, inhibiting their ability to differentiate. Our data suggest that losartan may be an effective treatment for the bone-associated dysmorphia displayed in OI whilst minimising potential adverse immune cell-related effects.

Summary

Osteoporosis and decreased bone density is a frequent complication of anorexia nervosa (AN). As of yet, there have been no studies of accomplished treatment of AN-related osteoporosis with romosuzumab, a monoclonal antibody to sclerostin. We report the first case of a premenopausal, 29-year old patient in Switzerland with decreased bone density and osteoporotic fractures due to anorexia nervosa, who completed the treatment with romosuzumab. There was a significant increase in bone mineral density (BMD) after 12 months of therapy. No serious side effects were reported. To date, only bisphosphonates, denosumab and teriparatide have been evaluated in treatment of AN-related osteoporosis in adolescents and premenopausal individuals respectively. Our report demonstrates that romosuzumab might be an alternative treatment option in patients with anorexia nervosa who are at high risk for osteoporotic fractures. To assess the efficacy and safety of romosuzumab in individuals with AN further studies are needed.

Vasorin (Vasn) is a pleiotropic molecule involved in various physiological and pathological conditions, including cancer. Vasn has also been detected in bone cells of developing skeletal tissues but no function for Vasn in bone metabolism has been implicated yet. Therefore, this study aimed to investigate if Vasn plays a significant role in bone biology. First, we investigated tissue distribution of Vasn expression, using lacZ knock-in reporter mice. We detected clear Vasn expression in skeletal elements of postnatal mice. In particular, osteocytes and bone forming osteoblasts showed high expression of Vasn, while the bone marrow was devoid of signal. Vasn knockout mice (Vasn^−/−) displayed postnatal growth retardation and died after four weeks. MicroCT analysis of femurs from 22- to 25-day-old Vasn^−/− mice demonstrated reduced trabecular and cortical bone volume corresponding to a low bone mass phenotype. Ex vivo bone marrow cultures demonstrated that osteoclast differentiation and activity were not affected by Vasn deficiency. However, osteogenesis of Vasn^−/− bone marrow cultures was disturbed, resulting in lower numbers of alkaline phosphate positive colonies, impaired mineralization and lower expression of osteoblast marker genes. In addition to the bone phenotype, these mice developed a vitamin D₃-related phenotype with a strongly reduced circulating 25-hydroxyvitamin D₃ and 1,25-dihydroxyvitamin D3 and urinary loss of vitamin D binding protein. In conclusion, Vasn-deficient mice suffer from severe disturbances in bone metabolism and mineral homeostasis.

Multicentric osteolysis nodulosis and arthropathy (MONA) is a rare skeletal dysplasia characterized primarily by progressive osteolysis, particularly affecting the carpal and tarsal bones, accompanied by osteoporosis. In addition, it features subcutaneous nodules on the palms and soles, along with the progressive onset of arthropathy, encompassing joint contractures, pain, swelling and stiffness. It is caused by a deficiency of the Matrix Metalloproteinase-2 (MMP2). In the current study we present a comprehensive clinical, radiological, genetic and in silico analysis of MONA in a consanguineous Pakistani family. Clinical and radiological examinations of the three severely affected siblings demonstrated a progressive MONA syndrome with phenotypic variability. The patients presented unusual facial appearance, thickened skin, severe short stature, short hands and feet. Radiographs revealed extensive bone deformities affecting upper and lower arms, legs, vertebrae and hip. Genetic analysis revealed a homozygous missense variant [c.539 A > T p.(Asp180Val)] in the MMP2 gene. In silico findings suggested a mutant MMP2 protein with a decreased stability and an altered pattern of interactions. Our findings add to the existing literature on the skeletal phenotype of MONA syndrome, including the specific clinical and radiological patterns observed. Moreover, the study will aid in genetic counseling and accurate diagnosis of families affected by the same disorder within the Pakistani population.