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Summary: The use of bone turnover marker (BTM) testing for patients with osteoporosis in the USA has not been well characterized. This retrospective US-based real-world data study found BTM testing has some association with treatment decision-making and lower fracture risk in patients with presumed osteoporosis, supporting its use in clinical practice. Introduction: The purpose of this study was to characterize bone turnover marker (BTM) testing patterns and estimate their clinical utility in treatment decision-making and fragility fracture risk in patients with osteoporosis using a retrospective claims database. Methods: Data from patients aged ≥ 50 years with newly diagnosed osteoporosis enrolled in the Truven MarketScan® Commercial Claims and Encounters and Medicare Supplemental and Co-ordination of Benefits databases from January 2008 to June 2018 were included. Osteoporosis was ascertained by explicit claims, fragility fracture events associated with osteoporosis, or prescribed anti-resorptive or anabolic therapy. BTM-tested patients were 1:1 propensity score matched to those untested following diagnosis. Generalized estimating equation models were performed to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for testing versus no testing on both treatment decision-making and fragility fracture. Results: Of the 457,829 patients with osteoporosis, 6075 were identified with ≥ 1 BTM test following diagnosis; of these patients, 1345 had a unique treatment decision made ≤ 30 days from BTM testing. The percentage of patients receiving BTM tests increased significantly each year (average annual % change: + 8.1%; 95% CI: 5.6–9.0; p = 0.01). Patients tested were significantly more likely to have a treatment decision (OR: 1.14; 95% CI: 1.13–1.15), and testing was associated with lower odds of fracture versus those untested (OR: 0.87; 95% CI: 0.85–0.88). Conclusion: In this large, heterogeneous population of patients with presumed osteoporosis, BTM testing was associated with treatment decision-making, likely leading to fragility fracture reduction following use. [ABSTRACT FROM AUTHOR]

Summary: A reduction in hip fracture incidence following population screening might reflect the effectiveness of anti-osteoporosis therapy, behaviour change to reduce falls, or both. This post hoc analysis demonstrates that identifying high hip fracture risk by FRAX was not associated with any alteration in falls risk. Introduction: To investigate whether effectiveness of an osteoporosis screening programme to reduce hip fractures was mediated by modification of falls risk in the screening arm. Methods: The SCOOP study recruited 12,483 women aged 70–85 years, individually randomised to a control (n = 6250) or screening (n = 6233) arm; in the latter, osteoporosis treatment was recommended to women at high risk of hip fracture, while the control arm received usual care. Falls were captured by self-reported questionnaire. We determined the influence of baseline risk factors on future falls, and then examined for differences in falls risk between the randomisation groups, particularly in those at high fracture risk. Results: Women sustaining one or more falls were slightly older at baseline than those remaining falls free during follow-up (mean difference 0.70 years, 95%CI 0.55–0.85, p < 0.001). A higher FRAX 10-year probability of hip fracture was associated with increased likelihood of falling, with fall risk increasing by 1–2% for every 1% increase in hip fracture probability. However, falls risk factors were well balanced between the study arms and, importantly, there was no evidence of a difference in falls occurrence. In particular, there was no evidence of interaction (p = 0.18) between baseline FRAX hip fracture probabilities and falls risk in the two arms, consistent with no impact of screening on falls in women informed to be at high risk of hip fracture. Conclusion: Effectiveness of screening for high FRAX hip fracture probability to reduce hip fracture risk was not mediated by a reduction in falls. [ABSTRACT FROM AUTHOR]

Data are scarce on the impact of vertebral fractures (VFX) on utility. The objective of this study was to assess the impact of prevalent and incident VFX on utility in both a patient-based and population-based sample. Data from the Multiple Outcomes of Raloxifene Evaluation (MORE) study ( n = 550 for prevalent VFX and n = 174 for incident VFX) and the European Prospective Osteoporosis Study (EPOS) ( n = 236) were used. Utility was assessed by the index score of the EQ-5D. In the MORE study, highly statistically significant associations were found between utility and the presence of prevalent VFX ( p < 0.001), number of prevalent VFX ( p < 0.001), severity of prevalent VFX ( p < 0.001), the combination of number and severity of prevalent VFX ( p = 0.001) and location of prevalent VFX ( p = 0.019). The mean utility was significantly lower among women who suffered an incident VFX (utility = 0.67) than among women who did not (utility = 0.77) ( p = 0.005), although utility loss was not significantly different between the two groups ( p = 0.142). In EPOS, the combination of number and severity of incident VFX was significantly related to utility ( p = 0.030). In conclusion, utility is lower among persons with prevalent and incident VFX, especially in a patient-based sample. Utility loss was not significantly different between women without and with incident VFX. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the currently available evidence for the effectiveness of bisphosphonates in children with low bone mineral density (BMD) and fragility fractures associated with juvenile idiopathic arthritis (JIA), and the safety of bisphosphonates in JIA and other conditions. Methods: Literature databases were searched using a structured search strategy. The effectiveness review included any studies of children with JIA treated with bisphosphonates. The safety review also included studies of osteogenesis imperfecta. Quantitative data analysis was not undertaken because of the heterogeneity of the studies; findings were summarised using tables and narrative synthesis. Results: Ninety four studies were identified. Sixteen studies (78 JIA children) were included in the effectiveness review: one randomised controlled trial, three controlled cohort studies, 11 case series, and one case report. At baseline, children had low BMD below the expected values for age and sex matched children. In all studies, treatment with bisphosphonates increased BMD compared with baseline: the mean percentage increase in spine BMD ranged from 4.5% to 19.1%. Overall, studies were heterogeneous and of variable quality. A total of 59 papers were included in the safety review; treatment durations were up to three years. The most common side effect was a flu-like reaction with intravenous treatment. This occurred during the first infusion and was transient; the symptoms were managed with paracetamol and did not occur during subsequent cycles. Conclusions: Bisphosphonates are a promising treatment for low BMD and fragility fractures in children with JIA. However, the quality of the current evidence is variable and better studies are needed to more clearly assess their role. [ABSTRACT FROM AUTHOR]

Introduction: It has been suggested that bone mineral density (BMD) measurements should be made at multiple sites, and that the lowest T-score should be taken for the purpose of diagnosing osteoporosis. Purpose: The aim of this study was to examine the use of BMD measurements at the femoral neck and lumbar spine alone and in combination for fracture prediction. Methods: We studied 19,071 individuals (68% women) from six prospective population-based cohorts in whom BMD was measured at both sites and fracture outcomes documented over 73,499 patient years. BMD values were converted to Z-scores, and the gradient of risk for any osteoporotic fracture and for hip fracture was examined by using a Poisson model in each cohort and each gender separately. Results of the different studies were merged using weighted β-coefficients. Results: The gradients of risk for osteoporotic fracture and for hip fracture were similar in men and women. In men and women combined, the risk of any osteoporotic fracture increased by 1.51 [95% confidence interval (CI) = 1.42-1.61] per standard deviation (SD) decrease in femoral-neck BMD. For measurements made at the lumbar spine, the gradient of risk was 1.47 (95% CI= 1.38-1.56). Where the minimum of the two values was used, the gradient of risk was similar (1.55; 95% CI=1.45-1.64). Higher gradients of risk were observed for hip fracture outcomes: with BMD at the femoral neck, the gradient of risk was 2.45 (95% CI=2.10-2.87), with lumbar BMD was 1.57 (95% CI=1.36-1.82), and with the minimum value of either femoral neck and lumbar spine was 2.11 (95% CI=1.81-2.45). Thus, selecting the lowest value for BMD at either the femoral neck or lumbar spine did not increase the predictive ability of BMD tests. By contrast, the sensitivity increased so that more individuals were identified but at the expense of specificity. Thus, the same effect could be achieved by using a less stringent T-score for the diagnosis of osteoporosis. Conclusion: Since taking the minimum value of the two measurements does not improve predictive ability, its clinical utility for the diagnosis of osteoporosis is low. [ABSTRACT FROM AUTHOR]

Population studies suggest that rib fractures are associated with a reduction in bone mass. While much is known about the predictive risk of hip, spine and distal forearm fracture on the risk of future fracture, little is known about the impact of rib fracture. The aim of this study was to determine whether a recalled history of rib fracture was associated with an increased risk of future limb fracture. Men and women aged 50 years and over were recruited from population registers in 31 European centres for participation in a screening survey of osteoporosis (European Prospective Osteoporosis Study). Subjects were invited to complete an interviewer-administered questionnaire that included questions about previous fractures including rib fracture, the age of their first fracture and also the level of trauma. Lateral spine radiographs were performed and the presence of vertebral deformity was determined morphometrically. Following the baseline survey, subjects were followed prospectively by annual postal questionnaire to determine the occurrence of clinical fractures. The subjects included 6,344 men, with a mean age of 64.2 years, and 6,788 women, with a mean age of 63.6 years, who were followed for a median of 3 years (range 0.4–5.9 years), of whom 135 men (2.3%) and 101 women (1.6%) reported a previous low trauma rib fracture. In total, 138 men and 391 women sustained a limb fracture during follow-up. In women, after age adjustment, those with a recalled history of low trauma rib fracture had an increased risk of sustaining ‘any’ limb fracture [relative hazard (RH) =2.3; 95% CI 1.3, 4.0]. When stratified by fracture type the predictive risk was more marked for hip (RH=7.7; 95% CI 2.3, 25.9) and humerus fracture (RH=4.5; 95% CI 1.4, 14.6) than other sites (RH=1.6; 95% CI 0.6, 4.3). Additional adjustment for prevalent vertebral deformity and previous (non-rib) low trauma fractures at other sites slightly reduced the strength of the association between rib fracture and subsequent limb fracture. In men, after age adjustment, there was a small though non-significant association between recalled history of rib fracture and future limb fracture. Our data highlight the importance of rib fracture as a marker of bone fragility in women. [ABSTRACT FROM AUTHOR]

The aim of this analysis was to determine the influence of lifestyle, anthropometric and reproductive factors on the subsequent risk of incident vertebral fracture in men and women aged 50–79 years. Subjects were recruited from population registers from 28 centers across Europe. At baseline, they completed an interviewer-administered questionnaire and had lateral thoraco-lumbar spine radiographs performed. Repeat spinal radiographs were performed a mean of 3.8 years later. Incident vertebral fractures were defined morphometrically and also qualitatively by an experienced radiologist. Poisson regression was used to determine the influence of the baseline risk factor variables on the occurrence of incident vertebral fracture. A total of 3173 men (mean age 63.1 years) and 3402 women (mean age 62.2 years) contributed data to the analysis. In total there were 193 incident morphometric and 224 qualitative fractures. In women, an age at menarche 16 years or older was associated with an increased risk of vertebral fracture (RR=1.80; 95%CI 1.24, 2.63), whilst use of hormonal replacement was protective (RR=0.58; 95%CI 0.34, 0.99). None of the lifestyle factors studied including smoking, alcohol intake, physical activity or milk consumption showed any consistent associations with incident vertebral fracture. In men and women, increasing body weight and body mass index were associated with a reduced risk of vertebral fracture though, apart from body mass index in men, the confidence intervals embraced unity. For most variables the strengths of the associations observed were similar using the qualitative and morphometric approaches to fracture definition. In conclusion our data suggest that modification of other lifestyle risk factors is unlikely to have a major impact on the population occurrence of vertebral fractures. The important biological mechanisms underlying vertebral fracture risk need to be explored using new investigational strategies. [ABSTRACT FROM AUTHOR]

: Bone mineral density (BMD) and hip axis length (HAL) are important determinants of fracture risk in women. There are, however, few data concerning their predictive risk in men. The aim of this study was to determine the relationship between BMD, HAL and the risk of hip fracture in men. A case–control design was used. Cases were men aged 50 years and over with a minimal-trauma hip fracture admitted to the Royal Cornwall Hospital, Truro, during 1995–1997. Controls were recruited from a large general practice within the catchment area of the hospital. Subjects were invited for assessment of BMD at the lumbar spine and proximal femur, using dual-energy X-ray absorptiometry. HAL was assessed using machine software. Data concerning BMD were available in 62 fracture cases and 100 controls. After adjusting for age, height and weight, a reduction in BMD was associated with a significant increase in the risk of hip fracture [odds ratio (OR) 1.8–4.0 per standard deviation (SD) reduction, depending on site]. HAL was similar in both fracture and control groups (12.0 cm vs 12.0 cm). After adjusting for height, there was no association between HAL and the risk of hip fracture (OR per 1 SD increase in HAL = 0.9; 95% confidence interval 0.6, 1.3). Compared with those with a cervical fracture (n= 31), those with an intertrochanteric fracture (n= 31) had lower BMD at all skeletal sites, though this was significant for the trochanteric site only. It is concluded that BMD though not hip axis length is a risk factor for low-trauma hip fracture in Caucasian men. [ABSTRACT FROM AUTHOR]

: In population-based studies of osteoporosis, ascertainment of fractures is typically based on self-report, with subsequent verification by medical records. The aim of this analysis was to assess the validity of self-report of incident nonspine fractures using a postal questionnaire. The degree of overreporting of fracture (false positives) was assessed by comparing self-reports of new fracture from respondents in the multicenter European Prospective Osteoporosis Study with data from other sources including radiographs and medical records. In the analysis, 563 subjects reported nonspine fractures. Verification of the presence of fracture was possible in 510 subjects. Of these, fractures were not confirmed in 11% (false positives). The percentage of false positives was greater in men than in women (15% vs 9%, p=0.04), and less for fractures of the distal forearm and hip than for fractures at other sites. In a separate study, the degree of underreporting (false negatives) was assessed by follow-up of 251 individuals with confirmed fracture ascertained from the records of fracture clinics in three European centers (Lubeck, Oviedo, Warsaw). Questionnaire responses were received from 174 (69%) subjects. Of these, 12 (7%) did not recall sustaining a fracture (false negatives). The percentage of false negatives was lower for hip and distal forearm fractures with only 3 of 90 (3%) such fractures not recalled. Using the combined data from both studies, of those who reported a ‘date’ of fracture on the questionnaire, 91% of subjects were correct to within 1 month of the actual date of the fracture. A postal questionnaire is a relatively simple and accurate method for obtaining information about the occurrence of hip and distal forearm fractures, including their timing. Accuracy of ascertainment of fractures at other sites is less good and where possible self-reported fractures at such sites should be verified from other sources. [ABSTRACT FROM AUTHOR]

A Correction to this paper has been published: https://doi.org/10.1007/s00198-021-05828-3 [ABSTRACT FROM AUTHOR]