Electronic search programs are effective in identifying patients with minimal trauma fractures.

We assessed two electronic search tools that screen medical records for documented fractures. Both programs reliably identified patients with any fracture but missed individuals with minimal trauma fracture to different degrees. A hybrid tool combining the methodology of both tools is likely to improve the identification of those with osteoporosis. PURPOSE: Most patients who suffer a minimal trauma fracture remain undiagnosed, placing them at high risk of refracture. Case finding can be improved by electronic search tools that screen medical records for documented fractures. Here, we assessed the efficacy of two new programs, AES and XRAIT, in identifying patients with minimal trauma fracture. METHODS: Each tool was applied to search the electronic medical record and/or radiology reports at two tertiary hospitals in Sydney, Australia, from 1 July to 31 December 2018. Samples of the extracted reports were then manually reviewed to determine the sensitivity of each program in detecting minimal trauma fractures. RESULTS: At the two centers, AES detected 872 and 1364 cases, whereas XRAIT identified 1414 and 2180 patients with fractures, respectively. The true positive rate for "any fracture" was similar for both instruments (77-88%). However, the ability to detect "minimal trauma fractures" differed between programs and centers (53-75% accuracy), with each tool identifying separate subsets of patients. Concordance between both tools was less than half of the combined total number of minimal trauma fractures (43-45%). Considering the total number of minimal trauma fractures detected by both tools combined, AES correctly identified 52-55% of cases while XRAIT identified 88-93% of cases. CONCLUSION: Both programs reliably identified patients with any fracture but missed individuals with minimal trauma fracture to different degrees. Hybrid tools combining the methodology of XRAIT and AES are likely to improve the identification of patients who require investigation and treatment for osteoporosis.

Disruption of glucocorticoid signalling in osteoblasts attenuates age-related surgically induced osteoarthritis.

OBJECTIVE: Aging is a major risk factor for osteoarthritis (OA). Skeletal expression and activity of the glucocorticoid-activating enzyme 11ß-hydroxysteroid-dehydrogenase type 1 increases progressively with age in humans and rodents. Here we investigated the role of endogenous osteocytic and osteoblastic glucocorticoid (GC) signalling in the development of osteoarthritic bone and cartilage damage in mice. METHODS: We utilized transgenic (tg) mice in which glucocorticoid signalling is disrupted in osteoblasts and osteocytes via overexpression of the glucocorticoid-inactivating enzyme, 11ß-hydroxysteroid-dehydrogenase type 2. Osteoarthritis was induced in 10- and 22-week-old male transgenic mice (tg-OA, n = 6/group) and their wildtype littermates (WT-OA, n = 7-8/group) by surgical destabilization of the medial meniscus (DMM). Sham-operated mice served as controls (WT- & tg-Sham, n = 3-5 and 6-8/group at 10- and 22-weeks of age, respectively). RESULTS: Sixteen weeks after DMM surgery, mice developed features of cartilage degradation, subchondral bone sclerosis and osteophyte formation. These changes did not differ between WT and tg mice when OA was induced at 10-weeks of age. However, when OA was induced at 22-weeks of age, cartilage erosion was significantly attenuated in tg-OA mice compared to WT-OA littermates. Similarly, subchondral bone volume (-5.2%, 95% confidence intervals (CI) -9.1 to -1.2%, P = 0.014) and osteophyte size (-4.0 mm2, 95% CI -7.5 to -0.5 mm2, P = 0.029) were significantly reduced in tg-OA compared to WT-OA mice. CONCLUSION: Glucocorticoid signalling in cells of the osteoblast lineage promotes the development of surgically-induced osteoarthritis in older, but not younger, male mice. These data implicate osteoblasts and osteocytes in the progression of DMM-OA, via a glucocorticoid-dependent and age-related pathway.

Barriers to secondary fracture prevention in primary care.

This study of current osteoporosis management patterns in general practice found that the majority of patients presenting to their local health practitioner with a recent low-trauma fracture was not managed appropriately. The analysis demonstrated that failure to investigate was highly predictive of failure to treat and that one of the major barriers to effective osteoporosis management is a lack of specific knowledge about who to investigate and treat. INTRODUCTION: Osteoporotic fractures are associated with significant morbidity and mortality. The current study aimed (i) to determine the number of patients with osteoporotic fractures who were not investigated or treated for osteoporosis by their primary care physician and (ii) to identify factors that contribute to the ongoing gap in osteoporosis care. METHODS: We conducted an observational retrospective study (2012-2014) using explicit medical record review at three major general practices in metropolitan Sydney. Patients aged 55 years or older who had a documented minimal trauma fracture (MTF) were identified. Data collected included demographics, prior fractures, testing for vitamin D/bone mineral density and initiation of osteoporosis pharmacotherapy. The main outcome measures included the number of patients who did not undergo the following: (i) a bone density scan, (ii) vitamin D measurement and/or (iii) initiation of osteoporosis pharmacotherapy. RESULTS: Of the 87 patients (69% female; mean age 71.7 years) with prevalent MTF, 55 (63%) were not referred for a bone density scan. Vitamin D levels were not measured in 36 patients (41%) and 55 patients (63%) did not receive specific osteoporosis pharmacotherapy. Failure to investigate was highly predictive of failure to treat (p < 0.001). The presence of major osteoporotic risk factors did not affect the likelihood of investigation or treatment, indicating that a major barrier to effective osteoporosis management was a lack of knowledge. CONCLUSION: Management of patients with MTF's in primary care is poor. Systems aimed at improving the identification and treatment of patients with osteoporotic fractures in this setting is required in order to close the osteoporosis care gap.

Cut-points for associations between vitamin D status and multiple musculoskeletal outcomes in middle-aged women.

This was the first study examining optimal vitamin D status for musculoskeletal health in middle-aged women. A 25-hydroxyvitamin D level of at least 29 to 33 nmol/L appears required for optimal musculoskeletal health, but the current cut-off of 50 nmol/L may be warranted. INTRODUCTION: This study aimed to determine whether cut-points exist for associations between serum 25-hydroxyvitamin D (25OHD) and musculoskeletal health outcomes in middle-aged women, below which greater 25OHD levels are associated with musculoskeletal health benefits and above which no such associations exist. METHODS: This is a cross-sectional study of 344 women aged 36-57 years. Cut-points for associations of serum 25OHD with lumbar spine (LS) and femoral neck (FN) bone mineral density (BMD), lower limb muscle strength (LMS), timed up and go test (TUG), functional reach test (FRT), lateral reach test (LRT), and step test (ST) were explored using locally weighted regression smoothing and nonlinear least-squares estimation, and associations above and below the identified cut-points were estimated using segmented regression. RESULTS: The prevalence of low 25OHD was 28 % (<50 nmol/L). Significant cut-points (nmol/L) were identified for FN BMD 31 (95 % confidence interval (CI): 18, 43), LS BMD 31 (17, 45), TUG 30 (24, 36), ST 33 (24, 31), FRT 31 (18, 43), and LMS 29 (8, 49) but not LRT (42 (-8, 93). Below these cut-points, there were beneficial associations between higher 25OHD level and each outcome, while above the cut-points, there were no beneficial associations. CONCLUSIONS: In middle-aged women, there are thresholds for associations between serum 25OHD concentrations and bone density and most balance measures, suggesting that 25OHD levels of at least 29 to 33 nmol/L are required for optimal musculoskeletal health in this population. The current cut-off of 50 nmol/L may be higher than needed for some outcomes but appears warranted overall.

Association of adipokines and joint biomarkers with cartilage-modifying effects of weight loss in obese subjects.

OBJECTIVES: To determine (1) the effects of weight loss in obese subjects on six adipokines and joint biomarkers; and (2) the relationship between changes in these markers with changes in cartilage outcomes. DESIGN: Plasma levels of adiponectin, leptin, IL-6, COMP, MMP-3 and urine levels of CTX-II were measured at baseline and 12 months from 75 obese subjects enrolled in two weight-loss programs. Magnetic resonance imaging (MRI) was used to assess cartilage volume and thickness. Associations between weight loss, cartilage outcomes and markers were adjusted for age, gender, baseline BMI, presence of clinical knee OA, with and without weight loss percent. RESULTS: Mean weight loss was 13.0 ± 9.5%. Greater weight loss percentage was associated with an increase in adiponectin (ß = 0.019, 95% CI 0.012 to 0.026,) and a decrease in leptin (ß = -1.09, 95% CI -1.37 to -0.82). Multiple regression analysis saw an increase in adiponectin associated with reduced loss of medial tibial cartilage volume (ß = 14.4, CI 2.6 to 26.3) and medial femoral cartilage volume (ß = 18.1, 95% CI 4.4 to 31.8). Decrease in leptin was associated with reduced loss of medial femoral volume (ß = -4.1, 95% CI -6.8 to -1.4) and lateral femoral volume (ß = -1.8, 95% CI -3.7 to 0.0). When weight loss percent was included in the model, only the relationships between COMP and cartilage volume remained statistically significant. CONCLUSIONS: Adiponectin and leptin may be associated with cartilage loss. Further work will determine the relative contributions of metabolic and mechanical factors in the obesity-related joint changes.

Predictors of re-fracture amongst patients managed within a secondary fracture prevention program: a 7-year prospective study.

SUMMARY: This 7-year prospective observational study determined the predictors of re-fracture amongst 234 patients managed within a Secondary Fracture Prevention programme. Poor compliance, multiple co-morbidities, corticosteroid therapy, low hip bone mineral density (BMD) or low body weight were all significantly associated with re-fracture in patients commenced on long-term anti-resorptive therapy. INTRODUCTION: Risk factors for osteoporotic fracture amongst treatment-naïve patients are well established. In contrast, predictors of re-fracture in patients optimally managed within a Secondary Fracture Prevention (SFP) programme are ill-defined. METHODS: This prospective observational study included 234 subjects with incident osteoporotic fractures managed long-term by the Concord SFP programme. Using Cox proportional hazards models, predictors of re-fracture were analysed separately for patients commenced on specific pharmacotherapy (group 1, N=171) and subjects receiving calcium and/or vitamin D supplements only (group 2, N=63). Relevant anthropometric, clinical and technical data were documented at each visit. Compliance and persistence were analysed as time-varying covariates. RESULTS: During a mean follow-up of 5.2 (range 3.5-7.3) years, 20.9% of all subjects re-fractured (26.3% in group 1, 6.3% in group 2). Multivariate predictors of re-fracture in group 1 were significant co-morbidity (HR 2.04 if >3, 95% CI 1.10-3.79, p=0.024), corticosteroid use (HR 1.75, 95% CI 1.12-2.73, p=0.013) and total hip BMD (HR 1.36 per 0.1 g/cm2 decrease, 95% CI 1.08-1.70, p=0.008). In contrast, gender, prevalent fractures and lumbar spine BMD were not associated with re-fracture. Amongst patients with complete compliance data, a medication possession ratio of ≤50% (HR 3.36, 95% CI 1.32-8.53, p=0.011) and low body weight (HR 1.04 per 1-kg decrease, 95% CI 1.003-1.08, p=0.032) were significantly associated with re-fracture. CONCLUSIONS: Amongst patients managed within a dedicated SFP programme, poor compliance, multiple co-morbidities, corticosteroid therapy, low hip BMD or low body weight are all associated with increased risk of re-fracture. This subgroup of patients therefore require intensive management including strategies to improve compliance.

Rapid biochemical response to denosumab in fibrous dysplasia of bone: report of two cases.

We report on the clinical and biochemical outcomes in two adult patients with active polyostotic fibrous dysplasia (FD) treated with the RANK-L inhibitor, denosumab, following unsatisfactory responses to prior long-term bisphosphonate therapy. A 44-year-old female (case 1) who had received a cumulative dose of 20 mg zoledronic acid over 2.5 years and a 48-year-old male (case 2) who had received a cumulative dose of 45 mg zoledronic acid over 8 years both experienced minimal reductions in pain scores and markers of bone turnover. Following initiation of denosumab 60 mg sc, changes in bone pain, bone turnover [assessed by serum amino-terminal propeptide of type I collagen (PINP) and urinary deoxypyridinoline] were monitored over a period of 20 and 8 months, respectively. Following administration of denosumab, both patients demonstrated a rapid and pronounced biochemical response: Within 4-7 weeks, bone turnover markers fell to levels within the respective reference range, and one patient reported a reduction in pain. Treatment with denosumab was well tolerated. However, transient asymptomatic hypocalcaemia and/or hypophosphatemia associated with a transient two to threefold increase in serum PTH levels was observed in both patients. Dosing intervals for denosumab varied significantly between the two patients, depending on disease activity at baseline. Denosumab appears to be effective in reducing bone turnover in adult patients with active FD. However, caution should be exercised, and patients should be monitored carefully as significant fluctuations in biochemical and hormonal indices can occur.

Compliance and persistence to oral bisphosphonate therapy following initiation within a secondary fracture prevention program: a randomised controlled trial of specialist vs. non-specialist management.

UNLABELLED: Following initiation of oral bisphosphonate therapy through a secondary fracture prevention program, 2-year treatment compliance and persistence remained high and were similar in patients randomised to follow-up by either the program or primary care physician. Thus, community-based and specialist management are equally effective in supporting compliance and persistence with anti-osteoporotic treatments. INTRODUCTION: The purpose of this study was to determine whether management by a secondary fracture prevention (SFP) program (aka "fracture liaison service") results in better compliance and persistence to oral bisphosphonate therapy than follow-up by the primary care physician, after initiation within an SFP program. METHODS: This prospective RCT included 102 patients with incident osteoporotic fractures referred to a SFP program in Sydney, Australia. Following oral bisphosphonate therapy initiation, patients were randomised to either 6-monthly follow-up with the SFP program (group A) or referral to their primary care physician with a single SFP program visit at 24 months (group B). Compliance and persistence to treatment were measured using pharmaceutical claims data. Predictors of compliance and persistence and associations between compliance and persistence, and changes in bone mineral density (BMD) or bone resorption marker, urinary deoxypyridinoline over 24 months were analysed. RESULTS: The median medication possession ratio at 24 months was 0.78 (IQR, 0.50-0.93) in group A and 0.79 (IQR, 0.48-0.96) in group B (p = 0.68). Persistence at 24 months was also similar in both groups (64 vs. 61%, respectively; p = 0.75). After adjusting for confounders, patients in group A were not more likely to be compliant (OR, 1.06; 95% CI, 0.46-2.47) or persistent (HR, 0.83; 95% CI, 0.27-1.67) than those randomised to group B. Time-based changes in BMD or bone turnover were not associated with compliance or persistence. CONCLUSION: Compliance and persistence to oral bisphosphonate therapy remain high amongst patients initiated within an SFP program, with community-based and SFP program management being equally effective in maintaining therapeutic compliance and persistence over 2 years. These results indicate that one of the main functions of an SFP program may be the initiation of therapy rather than continuous patient monitoring.

Models of care for the secondary prevention of osteoporotic fractures: a systematic review and meta-analysis.

Most people presenting with incident osteoporotic fractures are neither assessed nor treated for osteoporosis to reduce their risk of further fractures, despite the availability of effective treatments. We evaluated the effectiveness of published models of care for the secondary prevention of osteoporotic fractures. We searched eight medical literature databases to identify reports published between 1996 and 2011, describing models of care for secondary fracture prevention. Information extracted from each publication included study design, patient characteristics, identification strategies, assessment and treatment initiation strategies, as well as outcome measures (rates of bone mineral density (BMD) testing, osteoporosis treatment initiation, adherence, re-fractures and cost-effectiveness). Meta-analyses of studies with valid control groups were conducted for two outcome measures: BMD testing and osteoporosis treatment initiation. Out of 574 references, 42 articles were identified as analysable. These studies were grouped into four general models of care-type A: identification, assessment and treatment of patients as part of the service; type B: similar to A, without treatment initiation; type C: alerting patients plus primary care physicians; and type D: patient education only. Meta-regressions revealed a trend towards increased BMD testing (p = 0.06) and treatment initiation (p = 0.03) with increasing intensity of intervention. One type A service with a valid control group showed a significant decrease in re-fractures. Types A and B services were cost-effective, although definition of cost-effectiveness varied between studies. Fully coordinated, intensive models of care for secondary fracture prevention are more effective in improving patient outcomes than approaches involving alerts and/or education only.

Predictors of the rate of BMD loss in older men: findings from the CHAMP study.

UNLABELLED: Though bone loss tends to accelerate with age there are modifiable factors that may influence the rate of bone loss even in very old men. INTRODUCTION: The aim of this 2-year longitudinal study was to examine potential predictors of change in total hip bone mineral density (BMD) in older men. METHODS: The Concord Health and Ageing in Men Project is a population-based study in Sydney, Australia. For this study, 1,122 men aged 70-97 years had baseline and follow-up measures of total hip BMD measured with dual X-ray absorptiometry. Data about mobility, muscle strength, balance, medication use, cognition, medical history and lifestyle factors were collected using questionnaires and clinical assessments. Serum 25-hydroxyvitamin D [25(OH)D] was also measured. Multivariate linear regression models were used to assess relationships between baseline predictors and change in BMD. RESULTS: Over a mean of 2.2 years, there was a mean annualised loss of total hip BMD of 0.006 g/cm(2)/year (0.6 %) and hip BMC of 0.14 g/year (0.3 %). Annual BMD loss accelerated with increasing age, from 0.4 % in men aged between 70 and 75 years, to 1.2 % in men aged 85+ years. In multivariate regression models, predictors of faster BMD loss were anti-androgen, thiazolidinedione and loop-diuretic medications, kidney disease, poor dynamic balance, larger hip bone area, older age and lower serum 25(OH)D. Factors associated with attenuated bone loss were walking for exercise and use of beta-blocker medications. Change in BMD was not associated with baseline BMD, smoking, alcohol consumption, BMI, frailty, or osteoarthritis. CONCLUSION: There was considerable variation in the rate of hip bone loss in older men. Walking, better balance and beta blockers may attenuate the acceleration of BMD loss that occurs with age.

Haem Iron Intake Is Associated with Increased Major Adverse Cardiovascular Events, All-Cause Mortality, Congestive Cardiac Failure, and Coronary Revascularisation in Older Men: The Concord Health and Ageing in Men Project.

BACKGROUND: Nutritional intake can influence major adverse cardiovascular events (MACE). Dietary iron is found in two forms: haem-iron (HI) only found in animal sources and non-haem iron (NHI) present mostly in plant sources. OBJECTIVE: We evaluated the associations between dietary iron intakes with MACE and iron status biomarkers. DESIGN: Prospective cohort study. SETTING: The Concord Health and Ageing in Men Project, Sydney, Australia. PARTICIPANTS: 539 community-dwelling older Australian men aged 75 years and older. METHODS: Men underwent nutritional assessment using a validated diet history questionnaire. Entries were converted to food groups and nutrients. The dietary calculation was used to derive HI and NHI intakes from total iron intakes. Analyses of iron intakes with iron status biomarkers were conducted using linear regression, and with MACE and individual endpoints were conducted using Cox regression. Five-point MACE comprised of all-cause mortality, myocardial infarction (MI), congestive cardiac failure (CCF), coronary revascularisation, and/or ischaemic stroke. Four-point MACE included the four endpoints of MI, CCF, coronary revascularisation, and/or ischaemic stroke, and excluded all-cause mortality. RESULTS: At a median of 5.3 (4.6 - 6.3) years follow-up, the incidences were: 31.2% (n = 168) five-point MACE, 17.8% (n = 96) four-point MACE excluding all-cause mortality, 20.1% (n = 111) all-cause mortality, 11.3% (n = 61) CCF, and 3.1% (n = 15) coronary revascularisation. In adjusted analyses, higher HI intake (per 1mg increment) was associated with increased five-point MACE (HR: 1.45 [95% CI: 1.16, 1.80, P = .001]), four-point MACE excluding all-cause mortality (HR: 1.64 [95% CI: 1.26, 2.15, P <.001]), all-cause mortality (HR: 1.51 [95% CI: 1.15, 1.99, P = .003]), CCF (HR: 2.08 [95% CI: 1.45, 2.98, P <.001]), and coronary revascularisation (HR: 1.89 [95% CI: 1.15, 3.10, P = .012]). Compared with the bottom tertile of NHI intake, the middle tertile of NHI intake was associated with reduced risk of all-cause mortality (HR: 0.56 [95% CI: 0.33, 0.96, P = .035]). Total iron intake was not associated with MACE and individual endpoints. Dietary iron intakes were not associated with serum iron and haemoglobin. CONCLUSION: Higher haem iron intake was independently associated with increased risks of five-point MACE, four-point MACE excluding all-cause mortality, all-cause mortality, CCF, and coronary revascularisation in older men over 5 years.

Cost-effectiveness of the Concord Minimal Trauma Fracture Liaison service, a prospective, controlled fracture prevention study.

UNLABELLED: We evaluated the cost-effectiveness of a fracture liaison service prospectively designed to have a parallel control group treated by standard care. The clinical effectiveness of this service was associated with an incremental cost-effectiveness ratio versus standard care of Australian dollars (AUD) 17,291 per quality-adjusted life year (QALY) gained. INTRODUCTION: Osteoporotic fractures are a major burden for national health services. The risk of re-fracture following an osteoporotic fracture is particularly high. In a study unique in prospectively having a control group treated by standard care, we recently demonstrated that a Minimal Trauma Fracture Liaison (MTFL) service significantly reduces the risk of re-fracture by 80%. Since the service involves greater use of resources, we have now evaluated whether it is cost-effective. METHODS: A Markov model was developed that incorporated fracture probabilities and resource utilization data (expressed in AUD) obtained directly from the 4-year MTFL service clinical study. Resource utilization, local cost and mortality data and fracture-related health utility data were used to calculate QALYs with the MTFL service and standard care. Main outcome measures were: additional costs of the MTFL service over standard care, the financial savings achieved through reduced fractures and changes in QALYs associated with reduced fractures calculated over a 10-year simulation period. Costs and QALYs were discounted at 5% annually. Sensitivity analyses quantified the effects of different assumptions of effectiveness and resource utilization associated with the MTFL service. RESULTS: The MTFL service improved QALYs by 0.089 years and led to increased costs of AUD 1,486 per patient versus standard care over the 10-year simulation period. The incremental cost-effectiveness ratio versus standard care was AUD 17,291 per QALY gained. Results were robust under all plausible assumptions. CONCLUSIONS: The MTFL service is a cost-effective intervention to reduce recurrent osteoporotic fractures.

Does increased sunlight exposure work as a strategy to improve vitamin D status in the elderly: a cluster randomised controlled trial.

SUMMARY: Sunlight exposure by improving vitamin D status could be a simple public health strategy in reducing falls among frail elder people. In a randomised controlled trial, adherence to sunlight exposure was low (median adherence, 26%) and no effect of increased UV exposure on falls risk was observed (incidence rate ratio (IRR) 1.06, P = 0.73). INTRODUCTION: This study aimed to determine whether increased sunlight exposure was effective to improve vitamin D status and reduce falls in the elderly. METHODS: In a cluster randomised controlled trial (NCT00322166 at ClinicalTrials.gov), 602 residents aged 70 or more (mean age, 86.4 years; 71% female) were recruited from 51 aged care facilities in Northern Sydney, Australia. Participants were randomised by facility to receive either increased sunlight exposure (additional 30-40 min/day in the early morning) with (UV+) or without (UV) calcium supplementation (600 mg/day) or neither (control) for a year. The co-primary endpoints were change in serum 25 hydroxy vitamin D (25OHD) and falls incidence after 12 months. RESULTS: Adherence to sunlight exposure was low (median adherence, 26%; IQR, 7%-45%). Serum 25OHD levels were low at baseline (median, 32.9 nmol/L) and increased only slightly depending on the number of sunlight sessions attended over 12 months (P = 0.04). During the study, 327 falls occurred in 111 (54%) subjects in the control group, 326 falls in 111 (58%) subjects in the UV only group and 335 falls in 108 (52%) subjects in the UV+ group. By intention-to-treat analysis, there was no significant effect of increased UV exposure on falls risk (IRR, 1.06; 95% CI, 0.76-1.48; P = 0.73). However, in 66 participants who attended ≥130 sessions per year (adherence, ≥50% of 260 sessions-five per week), falls were significantly reduced (IRR, 0.52; 95% CI, 0.31-0.88; P = 0.01) compared with the control group. CONCLUSIONS: Increased sunlight exposure did not reduce vitamin D deficiency or falls risk in frail older people. This public health strategy was not effective most likely due to poor adherence to the intervention.

The effects of bed-rest and countermeasure exercise on the endocrine system in male adults: evidence for immobilization-induced reduction in sex hormone-binding globulin levels.

BACKGROUND AND AIM: There is limited data on the effects of inactivity (prolonged bed-rest) on parameters of endocrine and metabolic function; we therefore aimed to examine changes in these systems during and after prolonged (56- day) bed-rest in male adults. SUBJECTS AND METHODS: Twenty healthy male subjects underwent 8 weeks of strict bed-rest and 12 months of follow-up as part of the Berlin Bed Rest Study. Subjects were randomized to an inactive group or a group that performed resistive vibration exercise (RVE) during bed-rest. All outcome parameters were measured before, during and after bed-rest. These included body composition (by whole body dual X-ray absorptiometry), SHBG, testosterone (T), estradiol (E2), PRL, cortisol (C), TSH and free T3 (FT3). RESULTS: Serum SHBG levels decreased in inactive subjects but remained unchanged in the RVE group (p<0.001). Serum T concentrations increased during the first 3 weeks of bed-rest in both groups (p<0.0001), while E2 levels sharply rose with re-mobilization (p<0.0001). Serum PRL decreased in the control group but increased in the RVE group (p=0.021). C levels did not change over time (p≥0.10). TSH increased whilst FT3 decreased during bed-rest (p all ≤0.0013). CONCLUSIONS: Prolonged bed-rest has significant effects on parameters of endocrine and metabolic function, some of which are related to, or counteracted by physical activity.

Targeted intervention reduces refracture rates in patients with incident non-vertebral osteoporotic fractures: a 4-year prospective controlled study.

UNLABELLED: In the present prospective controlled observational study, we investigated the effect of a coordinated intervention program on 4-year refracture rates in patients with recent osteoporotic fractures. Compared to standard care, targeted identification, and management significantly reduced the risk of refracture by more than 80%. INTRODUCTION: The risk of refracture following an incident osteoporotic fracture is high. Despite the availability of treatments that reduce refracture and mortality rates, most patients with minimal trauma fracture (MTF) are not managed appropriately. The present prospective controlled observational study investigated the effect of a coordinated intervention program on 4-year refracture rates and time to refracture in patients with recent osteoporotic fractures. METHODS: Patients presenting with a non-vertebral MTF were actively identified and offered referral to a dedicated intervention program. Patients attending the clinic underwent a standardized set of investigations, were treated as indicated and reviewed at 12-monthly intervals ('MTF group'). Patients who elected to follow-up with their primary care physician were assigned to the concurrent control group. RESULTS: Groups were balanced for baseline anthropometric, socio-economic, and clinical risk factors. Over 4 years, 10 out of 246 patients (4.1%) in the MTF group and 31 of 157 patients (19.7%) in the control group suffered a new fracture, with a median time to refracture of 26 and 16 months, respectively (p < 0.01). Compared to the intervention group, the risk of refracture was increased by 5.3-fold in the control group (95% CI: 2.8-12.2, p < 0.01), and remained elevated (HR 5.63, 95%CI 2.73-11.6, p < 0.01) after adjustment for other significant predictors of refracture such as age and body weight. CONCLUSIONS: In patients presenting with a minimal trauma non-vertebral fracture, active identification and management significantly reduces the risk of refracture (Australian New Zealand Clinical Trials Registry ACTRN 12606000108516).

Oral bisphosphonates are associated with reduced mortality in frail older people: a prospective five-year study.

UNLABELLED: In a study of 2005 institutionalized older people, use of oral bisphosphonates was associated with a 27% reduction in risk of death compared to non-users after adjusting for potential confounders. INTRODUCTION: This study investigated whether reductions in mortality reported in a trial of intravenous zoledronate after hip fracture could be seen in older people taking oral bisphosphonates. METHODS: Two thousand and five institutionalized older people (mean age 85.7 years) were assessed at baseline and followed up for hip fracture and death for at least 5 years. Cox proportional hazards regression was used to estimate effects of bisphosphonates on risk of death. RESULTS: At baseline, 78 subjects were taking oral bisphosphonates. Over 5 years of follow-up, 1,596 participants (80%) died. Use of bisphosphonates was associated with a 27% reduction in risk of death compared to non-users after adjusting for age, gender, type of institution, immobility, number of medications, weight, cognitive function, co-morbidities, and hip fracture incidence during the follow-up period (hazard ratio 0.73; 95% CI, 0.56 to 0.94; P = 0.02). CONCLUSION: Oral bisphosphonates are associated with a reduction in the risk of death in the elderly. The mechanism of effect requires further investigation.

Lifestyle factors, medications, and disease influence bone mineral density in older men: findings from the CHAMP study.

UNLABELLED: Aging alone is not the only factor accounting for poor bone health in older men. There are modifiable factors and lifestyle choices that may influence bone health and result in higher bone density and lower fracture risk even in very old men. INTRODUCTION: The aim of this cross-sectional analysis was to identify the factors associated with areal bone mineral density (BMD) and their relative contribution in older men. METHODS: The Concord Health and Ageing in Men Project is a population-based study in Sydney, Australia, involving 1,705 men aged 70-97. Data were collected using questionnaires and clinical assessments. BMD of the hip and spine was measured by dual X-ray absorptiometry. RESULTS: In multivariate regression models, BMD of the hip was associated with body weight and bone loading physical activities, but not independently with age. The positive relationship between higher BMD and recreational activities is attenuated with age. Factors independently associated with lower BMD at the hip were inability to stand from sitting, a history of kidney stones, thyroxine use, and Asian birth and at the spine, chronic obstructive pulmonary disease, paternal fracture history, and thyroxine use. Higher body weight, participation in dancing, tennis or jogging, quadriceps strength, alcohol consumption, and statin use were associated with higher hip BMD, while older age, osteoarthritis, higher body weight, and aspirin use were associated with higher spinal BMD. CONCLUSION: Maintaining body weight, physical activity, and strength were positively associated with BMD even in very elderly men. Other parameters were also found to influence BMD, and once these were included in multivariate analysis, age was no longer associated with BMD. This suggests that age-related diseases, lifestyle choices, and medications influence BMD rather than age per se.

Socioeconomic status and bone health in community-dwelling older men: the CHAMP Study.

SUMMARY: The association between socioeconomic status (SES) and bone health, specifically in men, is unclear. Based upon data from the large prospective Concord Health in Ageing Men Project (CHAMP) Study of community-dwelling men aged 70 years or over, we found that specific sub-characteristics of SES, namely, marital status, living circumstances, and acculturation, reflected bone health in older Australian men. INTRODUCTION: Previous studies reported conflicting results regarding the relationship between SES and bone health, specifically in men. The main objective of this study was to investigate associations of SES with bone health in community-dwelling men aged 70 years or over who participated in the baseline phase of the CHAMP Study in Sydney, Australia. METHODS: The Australian Socioeconomic Index 2006 (AUSEI06) based on the Australian and New Zealand Standard Classification of Occupations was used to determine SES in 1,705 men. Bone mineral density and bone mineral content (BMC) were determined by dual-energy X-ray absorptiometry. Bone-related biochemical and hormonal parameters, including markers of bone turnover, parathyroid hormone, and vitamin D, were measured in all men. RESULTS: General linear models adjusted for age, weight, height, and bone area revealed no significant differences across crude AUSEI06 score quintiles for BMC at any skeletal site or for any of the bone-related biochemical measures. However, multivariate regression models revealed that in Australian-born men, marital status was a predictor of higher lumbar BMC (ß = 0.07, p = 0.002), higher total body BMC (ß = 0.05, p = 0.03), and lower urinary NTX-I levels (ß=-0.08, p = 0.03), while living alone was associated with lower BMC at the lumbar spine (ß=-0.05, p = 0.04) and higher urinary NTX-I levels (ß=0.07, p = 0.04). Marital status was also a predictor of higher total body BMC (ß = 0.14, p = 0.003) in immigrants from Eastern and South Eastern Europe. However, in immigrants from Southern Europe, living alone and acculturation were predictors of higher femoral neck BMC (ß = 0.11, p = 0.03) and lumbar spine BMC (ß = 0.10, p = 0.008), respectively. CONCLUSIONS: Although crude occupation-based SES scores were not significantly associated with bone health in older Australian men, specific sub-characteristics of SES, namely, marital status, living circumstances, and acculturation, were predictors of bone health in both Australia-born men and European immigrants.

Circulating Sex Steroid Measurements of Men by Mass Spectrometry Are Highly Reproducible after Prolonged Frozen Storage.

Long-term studies investigating hormone-dependent cancers and reproductive health often require prolonged frozen storage of serum which assumes that the steroid molecules and measurements are stable over that time. Previous studies of reproducibility of circulating steroids have relied upon flawed historical rather than contemporaneous controls. We measured serum testosterone (T), dihydrotestosterone (DHT), estradiol (E2) and estrone (E1) in 150 randomly selected serum samples by liquid chromatography-mass spectrometry (LC-MS) from men 70 years or older (mean age 77 years) in the CHAMP study. The original measurements in 2009 were repeated 10 years later using the identical serum aliquot (having undergone 2-4 freeze-thaw cycles in the interim) in 2019 together with another never-thawed aliquot of the same serum sample. The results of all three sets of measurements were evaluated by Passing-Bablok regression and Bland-Altman difference analysis. Serum androgens (T, DHT) and estrogens (E2, E1) measured by LC-MS display excellent reproducibility when stored for 10 years at -80 C without thawing. Serum T and DHT displayed high level of reproducibility across all three sets of measurements. Multiple freeze-thaw cycles over those storage conditions do not significantly affect serum T, DHT and E1 concentrations but produce a modest increase (21%) in serum E2 measurements.

Frailty and Cause-Specific Hospitalizations in Community-Dwelling Older Men.

OBJECTIVES: The types of medical conditions leading to hospitalization in frail older people have not been investigated. The objectives were to evaluate associations between frailty and (a) risk of all-cause and cause-specific hospitalization, and (b) rate of all-cause and cause-specific hospitalizations. DESIGN, SETTING AND PARTICIPANTS: Community-dwelling men aged 70+ years in the Concord Health and Ageing in Men Project (CHAMP) were assessed for frailty at baseline (2005-2007, n=1705). MEASUREMENTS: Frailty was determined by both the Fried frailty phenotype (FP) and the Rockwood frailty index (FI). Non-elective and elective hospitalization data were accessed from the New South Wales (NSW) Admitted Patient Data Collection and mortality from the NSW Deaths Registry for the period 2005-2017. Causes of hospitalization were categorized using ICD-10 classification of principal diagnoses based on organ system involved into 14 major categories. RESULTS: Nearly 80% of CHAMP men had at least one non-elective hospitalization and 63% had an elective hospitalization over a 9-year follow-up. Men with FP frailty were twice as likely to have a non-elective hospitalization (HR: 1.98, 95%CI: 1.61-2.44) and a greater number of non-elective hospitalizations (IRR: 1.44, 95%CI: 1.22-1.70). Similar relationships were found between FI frailty and non-elective hospitalizations. Men with frailty (either FP or FI) were more likely to have at least one non-elective hospitalization for 13 of the 14 cause-related admissions. In contrast, frailty was only associated with 3 cause-related elective hospitalizations. Men with frailty were also more likely to have an increased number of non-elective hospitalizations for all 14 causes, but only for 6 causes of elective hospitalizations. CONCLUSIONS: Our findings suggest frailty increases the risk and number of non-elective hospitalizations in older men for a wide range of cause. Strategies on early identification of frailty, followed by appropriate preventative strategies to lower the risk of non-elective hospital admissions are warranted.