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.
Summary 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).
Summary
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.
Summary
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.
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.
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•Reproducibility of steroid measurement in long-term frozen storage is crucial for long-term epidemiological research studies.•Using liquid chromatography mass spectrometry serum ...testosterone, dihydrotestosterone estradiol and estrone were highly reproducible after 10 years unthawed frozen storage as well as after multiple freeze-thaw cycles, apart from small increases in serum estradiol.
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.
When subjects are selected on the basis of fall risk alone, therapies for osteoporosis have not been effective. In a prospective study of elderly subjects at high risk of falls, we investigated the ...influence of bone strength and fall risk on fracture.
At baseline we assessed calcaneal bone ultrasound attenuation (BUA) as well as quantitative measures of fall risk in 2005 subjects in residential care. Incident falls and fractures were recorded (median follow-up 705 days).
A total of 6646 fall events and 375 low trauma fracture events occurred. The fall rate was 214 per 100 person years and the fracture rate 12.1 per 100 person years. 82% of the fractures could be attributed to falls. Although fracture rates increased with decreasing BUA (incidence rate ratio 1.94 for lowest vs. highest BUA tertile, p<0.002), incident falls also affected fracture incidence. Subjects who fell frequently (>3.15 falls/per person year) were 3.35 times more likely to suffer a fracture than those who did not fall. Some fall risk factors such as balance were associated with the lowest fracture risk lowest in the worst performing group. Multivariate analysis revealed higher fall rate, history of previous fracture, lower BUA, lower body weight, cognitive impairment and better balance as significant independent risk factors for fracture.
In the frail elderly, both skeletal fragility and fall risk including the frequency of exposure to falls are important determinants of fracture risk.
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.
Summary
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.
Summary
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.
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