Lower Fracture Risk Research Articles

Dietary recommendations in the prevention and treatment of osteoporosis.

This article presents the initial recommendations of the French Rheumatology Society (Société Française de Rhumatologie - SFR) and the Osteoporosis Research and Information Group (Groupe de Recherche et d'Informations sur les Ostéoporoses - GRIO) on the role of diet in the prevention and treatment of osteoporosis. The recommendations were produced by a working group composed of rheumatologists, physician nutrition specialists and a geriatrician. Fifteen (15) questions pertaining to "daily practices" were preselected by the working group. For the literature review, the working group focussed mainly on the effects of diet on bone mineral density (BMD) and fractures, and primarily on meta-analyses of longitudinal studies and dietary intervention studies. A Mediterranean-type diet and the daily consumption of 2 to 3 dairy products are recommended. Together, these provide the calcium and "high quality" protein required to maintain a normal calcium-phosphorus balance and bone metabolism, and are associated with lower fracture risk. Conversely, unbalanced Western diets, vegan diets, weight-loss diets in non-overweight individuals, alcohol consumption and daily consumption of sodas are advised against. In terms of the beneficial effects on bone mineral density and fracture risk, current scientific data are either insufficient or too divergent to recommend increasing or restricting the consumption of tea or coffee, vitamins other than vitamin D, vitamin D-enriched or phytoestrogen-rich foods, calcium-enriched plant-based beverages, oral nutritional supplements, or dietary sources of prebiotics and probiotics. These are the first set of recommendations addressing the role of diet in the prevention and treatment of osteoporosis. More research is necessary to direct and support guidelines.

Association between statin use and fractures among dialysis patients in the north of the West Bank in 2021

IntroductionHip fractures are associated with higher morbidity and mortality among dialysis patients than among the general population. Statins reduce the risk of hip and bone fractures. However, this protective effect has not been studied in dialysis patients. MethodsHemodialysis patients from hemodialysis centers located in the north of the West Bank were recruited (N ​= ​713) in a cross-sectional study in 2021. A statin user is a patient who has used statin for at least one year. The patient's medical records and an interview-administered structured questionnaire were used. Adjusted multiple logistic regression examined the association between statin use and fractures. A p-value less than 0.05 was considered statistically significant. ResultsThe final sample size was 529 patients, 184 were excluded, 60.7% were males, 54.4% were statin users, 76.1% were always adherent to their statin, and 75.3% used moderate-intensity statin. Statin users who were always adherent to their dose had a significantly lower risk of hip fractures (OR ​= ​0.090, p-value ​= ​0.026) than rarely adherent patients. In addition, patients who were always adherent with their statin dose (OR ​= ​0.188, p-value ​= ​0.007) or sometimes adherent (OR ​= ​0.171, p-value ​= ​0.022) had a significantly lower risk of having other bone fractures after dialysis than the rarely adherent counterparts. There were no differences between high and moderate-intensity statins regarding hip fracture effects (p-value >0.05). Moreover, the increased duration of dialysis significantly increased the risk of hip fractures (OR ​= ​1.349, p-value ​= ​0.003). ConclusionThe results of this study suggest that adherence to statin therapy was associated with decreased risk of hip fractures and other bone fractures among hemodialysis patients. These results could be the initial evidence of the protective effect against a vital health hazard among dialysis patients. This might ultimately contribute to re-considering the current statins prescription practice for dialysis patients. Further studies are recommended.

Time-varying exposure to anti-osteoporosis drugs and risk of first-time hip fracture: a population wide study within the Norwegian Epidemiologic Osteoporosis Studies (NOREPOS)

SummaryWe investigated the association between bisphosphonate and denosumab use and risk of hip fracture in Norway. These drugs protect against fractures in clinical trials, but their population-level effect is unknown. Our results showed lowered risk of hip fracture for treated women. Treatment of high-risk individuals could prevent future hip fractures.PurposeTo investigate whether bisphosphonates and denosumab reduced the risk of first-time hip fracture in Norwegian women when adjusting for a medication-based comorbidity index.MethodsNorwegian women aged 50–89 in 2005–2016 were included. The Norwegian prescription database (NorPD) supplied data on exposures to bisphosphonates, denosumab, and other drugs for the calculation of the Rx-Risk Comorbidity Index. Information on all hip fractures treated in hospitals in Norway was available. Flexible parametric survival analysis was used with age as time scale and with time-varying exposure to bisphosphonates and denosumab. Individuals were followed until hip fracture or censoring (death, emigration, age 90 years), or 31 December 2016, whichever occurred first. Rx-Risk score was included as a time-varying covariate. Other covariates were marital status, education, and time-varying use of bisphosphonates or denosumab with other indications than osteoporosis.ResultsOf 1,044,661 women 77,755 (7.2%) were ever-exposed to bisphosphonate and 4483 (0.4%) to denosumab. The fully adjusted hazard ratios (HR) were 0.95 (95% confidence interval (CI): 0.91–0.99) for bisphosphonate use and 0.60 (95% CI: 0.47–0.76) for denosumab use. Bisphosphonate treatment gave a significantly reduced risk of hip fracture compared with the population after 3 years and denosumab after 6 months. Fracture risk was lowest in denosumab users who had previously used bisphosphonate: HR 0.42 (95% CI: 0.29–0.61) compared with the unexposed population.ConclusionsIn population-wide real-world data, women exposed to bisphosphonates and denosumab had a lower hip fracture risk than the unexposed population after adjusting for comorbidity. Treatment duration and treatment history impacted fracture risk.

Effect of adipokine and ghrelin levels on BMD and fracture risk: an updated systematic review and meta-analysis.

Circulating adipokines and ghrelin affect bone remodeling by regulating the activation and differentiation of osteoblasts and osteoclasts. Although the correlation between adipokines, ghrelin, and bone mineral density (BMD) has been studied over the decades, its correlations are stillcontroversial. Accordingly, an updated meta-analysis with new findings is needed. This study aimed to explore the impact of serum adipokine and ghrelin levels on BMD and osteoporotic fractures through a meta-analysis. Studies published till October 2020 in Medline, Embase, and the Cochrane Library were reviewed. We included studies that measured at least one serum adipokine level and BMD or fracture risk in healthy individuals. We excluded studies with one or more of the following: patients less than 18 years old, patients with comorbidities, who had undergone metabolic treatment, obese patients, patients with high physical activities, and a study that did not distinguish sex or menopausal status. We extracted the data that include the correlation coefficient between adipokines (leptin, adiponectin, and resistin) and ghrelin and BMD, fracture risk by osteoporotic status from eligible studies. A meta-analysis of the pooled correlations between adipokines and BMD was performed, demonstrating that the correlation between leptin and BMD was prominent in postmenopausal women. In most cases, adiponectin levels were inversely correlated with BMD. A meta-analysis was conducted by pooling the mean differences in adipokine levels according to the osteoporotic status. In postmenopausal women, significantly lower leptin (SMD = -0.88) and higher adiponectin (SMD = 0.94) levels were seen in the osteoporosis group than in the control group. By predicting fracture risk, higher leptin levels were associated with lower fracture risk (HR = 0.68), whereas higher adiponectin levels were associated with an increased fracture risk in men (HR = 1.94) and incident vertebral fracture in postmenopausal women (HR = 1.18). Serum adipokines levels can utilize to predict osteoporotic status and fracture risk of patients. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021224855, identifier CRD42021224855.

Radiotherapy-related insufficiency fractures and bone mineral density: what is the connection?

Radiotherapy-related insufficiency fractures (RRIFs) represent a common, burdensome consequence of pelvic radiotherapy. Their underlying mechanisms remain unclear, and data on the effect of osteoporosis are contradictory, with limited studies assessing bone mineral density (BMD) by dual-energy x-ray absorptiometry (DXA). BMD by DXA (Hologic) scan and fracture risk following pelvic RRIF were retrospectively assessed in 39 patients (median age 68 years) at a tertiary cancer centre. Patient characteristics and treatment history are presented narratively; correlations were explored using univariate regression analyses. Additional cancer treatments included chemotherapy (n = 31), surgery (n = 20) and brachytherapy (n = 19). Median interval between initiation of radiotherapy and RRIF was 11 (7.5-20.8) and that between RRIF and DXA 3 was (1-6) months. Three patients had normal BMD, 16 had osteopenia and 16 osteoporosis, following World Health Organization classification. Four patients were <40 years at the time of DXA (all Z-scores > -2). Median 10-year risk for hip and major osteoporotic fracture was 3.1% (1.5-5.7) and 11.5% (7.1-13.8), respectively. Only 33.3% of patients had high fracture risk (hip fracture >4% and/or major osteoporotic >20%), and 31% fell above the intervention threshold per National Osteoporosis Guidelines Group (NOGG) guidance (2017). Higher BMD was predicted by lower pelvic radiotherapy dose (only in L3 and L4), concomitant chemotherapy and higher body mass index. At the time of RRIF, most patients did not have osteoporosis, some had normal BMD and overall had low fracture risk. Whilst low BMD is a probable risk factor, it is unlikely to be the main mechanism underlying RRIFs, and further studies are required to understand the predictive value of BMD.

Associations of Lean Mass, Muscular Strength, and Physical Function with Trabecular Bone Score in Older Adults

Introduction/Background: Trabecular bone score (TBS) is an indirect measurement of bone quality and microarchitecture determined from dual-energy X-ray absorptiometry (DXA) imaging of the lumbar spine. TBS predicts fracture risk independent of bone mass/density, suggesting this assessment of bone quality adds value to the understanding of patients’ bone health. While lean mass and muscular strength have been associated with higher bone density and lower fracture risk among older adults, the literature is limited regarding the relationship of lean mass and strength with TBS. The purpose of this study was to determine associations of DXA-determined total body and trunk lean mass, maximal muscular strength, and gait speed as a measure of physical function, with TBS in 141 older adults (65-84 yr, 72.5 +/- 5.1 yr, 74% women). Methodology: Assessments included lumbar spine (L1-L4) bone density and total body and trunk lean mass by DXA, lower body (leg press) and upper body (seated row) strength by one repetition maximum tests, hand grip strength, and usual gait speed. TBS was derived from the lumbar spine DXA scan. Multivariable linear regression determined the contribution of proposed predictors to TBS. Results: After adjusting for age, sex, and lumbar spine bone density, upper body strength significantly predicted TBS (unadjusted/adjusted R2= 0.16/ 0.11, β coefficient =0.378, p=0.005), while total body lean mass index showed a trend in the expected direction (β coefficient =0.243, p=0.053). Gait speed and grip strength were not associated with TBS (p>0.05). Conclusion: Maximum strength of primarily back muscles measured as the seated row appears important to bone quality as measured by TBS, independent of bone density. Additional research on exercise training targeting back strength is needed to determine its clinical utility in preventing vertebral fractures among older adults.

Fracture risk in women with osteoporosis initiated on gastro-resistant risedronate versus immediate release risedronate or alendronate: a claims data analysis in the USA

SummaryThe study results indicate that women with osteoporosis initiated on gastro-resistant risedronate have a lower risk of fracture than those initiated on immediate release risedronate or alendronate. A large proportion of women discontinued all oral bisphosphonate therapies within 1 year of treatment start.PurposeUsing a US claims database (2009–2019), we compared risk of fractures between women with osteoporosis initiated on gastro-resistant (GR) risedronate and those initiated on (a) immediate release (IR) risedronate or (b) immediate release alendronate.MethodsWomen aged ≥ 60 years with osteoporosis who had ≥ 2 oral bisphosphonate prescription fills were followed for ≥ 1 year after the first observed bisphosphonates dispensing (index date). Fracture risk was compared between the GR risedronate and IR risedronate/alendronate cohorts using adjusted incidence rate ratios (aIRRs), both overall and in subgroups with high fracture risk due to older age or comorbidity/medications. Site-specific fractures were identified based on diagnosis codes recorded on medical claims using a claims-based algorithm. Persistence on bisphosphonate therapy was evaluated for all groups.ResultsaIRRs generally indicated lower fracture risk for GR risedronate than IR risedronate and alendronate. When comparing GR risedronate to IR risedronate, statistically significant aIRRs (p < 0.05) were observed for pelvic fractures in the full cohorts (aIRRs = 0.37), for any fracture and pelvic fractures among women aged ≥ 65 years (aIRRs = 0.63 and 0.41), for any fracture and pelvic fractures among women aged ≥ 70 years (aIRRs = 0.69 and 0.24), and for pelvic fracture among high-risk women due to comorbidity/medications (aIRR = 0.34). When comparing GR risedronate to alendronate, statistically significant aIRRs were observed for pelvic fractures in the full cohorts (aIRR = 0.54), for any fracture and wrist/arm fractures among women aged ≥ 65 years (aIRRs = 0.73 and 0.63), and for any fracture, pelvic, and wrist/arm fractures among women aged ≥ 70 years (aIRRs = 0.72, 0.36, and 0.58). In all cohorts, ~ 40% completely discontinued oral bisphosphonates within 1 year.ConclusionsDiscontinuation rates of oral bisphosphonate therapy were high. However, women initiated on GR risedronate had a significantly lower risk of fracture for several skeletal sites than women initiated on IR risedronate/alendronate, particularly those aged ≥ 70 years.

Examining agreement between finite element modelling methodologies in predicting pathological fracture risk in proximal femurs with bone metastases

BackgroundFinite element modelling methodologies available for assessing femurs with metastases accurately predict strength and pathological fracture risk which has led them to being considered for implementation into the clinic. However, the models available use varying material models, loading conditions, and critical thresholds. The aim of this study was to determine the agreement between finite element modelling methodologies in assessing fracture risk in proximal femurs with metastases. MethodsCT images of the proximal femur were obtained of 7 patients who presented with a pathologic femoral fracture (fracture group) and the contralateral femur of 11 patients scheduled for prophylactic surgery (non-fracture group). Fracture risk was predicted for each patient following three established finite modelling methodologies which have previously shown to accurately predict strength and determine fracture risk: non-linear isotropic -based model, strain fold ratio -based model, Hoffman failure criteria -based model. FindingsThe methodologies demonstrated good diagnostic accuracy in assessing fracture risk (AUC = 0.77, 0.73, and 0.67). There was a stronger monotonic association between the non-linear isotropic and Hoffman -based models (τ = 0.74) than with the strain fold ratio model (τ = −0.24 and − 0.37). There was moderate or low agreement between methodologies in discriminating between individuals at high or low risk of fracture (κ = 0.20, 0.39, and 0.62). InterpretationThe present results suggest there may be a lack of consistency in the management of pathological fractures in the proximal femur based on the finite element modelling methodologies.

Relationships between Obesity and Incidence of Fractures in a Middle-Aged Population: A Study from the CARTaGENE Cohort.

The association between obesity and fracture risk is complex and may vary by definition of obesity, skeletal site, and sex. We aimed to evaluate the relationships between obesity, defined using body mass index (BMI) or waist circumference (WC), and fracture incidence at any site and by skeletal site (i.e., major osteoporotic fractures [MOFs], distal lower limb fractures [tibia, ankle, feet], and distal upper limb fractures [forearm/elbow, wrist]). The secondary aim was to assess the aforementioned relationships by sex. We used CARTaGENE, a large population-based cohort of individuals aged 40-70 years from Quebec, Canada, who were assessed in 2009-2010. Incident fractures were identified via linkage with healthcare administrative databases over a 7-year period. Cox proportional hazard models adjusted for several potential confounders were used to estimate the relationships, with exposures treated as continuous variables. Results are reported as adjusted hazard ratios (aHRs) and 95% confidence intervals. We identified 19 357 individuals (mean ± standard deviation: age 54 ± 8 years, BMI 27 ± 5 kg/m2, WC 94 ± 14 cm; 51.6% women). During follow-up, 497 women and 323 men sustained a fracture. There was a linear relationship between fracture incidence and WC, while cubic splines best fitted the relationship for BMI. Greater WC was associated with an increased risk of fracture at the distal lower limbs in the whole cohort and in the subgroup of women: aHR for each 10 cm increased in WC of 1.12 (1.03, 1.21) and 1.12 (1.01, 1.24), respectively. In men, WC was not significantly associated with any fracture outcome. Higher BMI was also significantly associated with distal lower limb fracture risk in the whole cohort (p=0.018). No significant relationships were found between either WC or BMI and the risk of any fracture, MOFs, and distal upper limb fractures. In middle-aged individuals, obesity, and mainly abdominal obesity, was associated with distal lower limb fracture risk. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Comparison of Fractures Among Older Adults Who Are Ambulatory vs Those Who Use Wheelchairs in Sweden

Several diseases and conditions, such as cerebrovascular disease, arthritis, previous fractures, neurological diseases, or amputation, can result in severe immobility justifying wheelchair use for increased mobility. Immobility results in disuse osteoporosis and is considered a risk factor for fracture, although there are no large cohort studies that have investigated fracture risk in patients who use wheelchairs compared with an ambulatory control group. To investigate whether immobilized adults who used wheelchairs had a different risk of fracture and injurious falls compared with matched ambulatory controls. This retrospective cohort study compared patients who used wheelchairs and controls (propensity score matched 1:1 using 22 variables relating to anthropometrics, general condition, comorbidity, and fall and fracture risk), identified through a national database of adults 65 years or older who underwent a health evaluation (baseline) at Swedish health care facilities. Patients were followed up from January 1, 2007, to December 31, 2017, and data analysis was performed between June 1 and 30, 2022. Incident fracture, injurious falls without fracture, and deaths. A total of 55 442 adults using wheelchairs were included in the analysis (mean [SD] age, 83.2 [8.3] years; 60.5% women). Those who used wheelchairs and the 55 442 matched controls were followed up for a median of 2.0 (IQR, 0.5-3.2) and 2.3 (IQR, 0.8-3.6) years, respectively. Patients who used wheelchairs had a lower risk of any fracture (hazard ratio [HR], 0.43 [95% CI, 0.41-0.44]), major osteoporotic fracture (HR, 0.32 [95% CI, 0.31-0.33]), and hip fracture (HR, 0.30 [95% CI, 0.28-0.32]) compared with the ambulatory controls, associations that were only marginally affected by multivariable (same as the matching variables) adjustment. The risk of fall injury was lower among those who used wheelchairs than among ambulatory controls (unadjusted HR for Cox proportional hazards models, 0.48 [95% CI, 0.47-0.50]) and remained highly similar after adjustments. Patients who used wheelchairs had a significantly increased risk of death (HR, 1.35 [95% CI, 1.33-1.36]) compared with controls. Association between wheelchair use and fracture outcomes and injurious falls, calculated using a Fine and Gray model with death as a competing risk, was similar to associations obtained using Cox proportional hazards regression for all fracture outcomes. In this retrospective cohort study of older adults, wheelchair use was associated with a lower risk of fracture than observed in ambulatory controls. These findings suggest that immobility associated with wheelchair use should not be considered a risk factor for fracture.

The proportion of Thai postmenopausal women who would be eligible for anti-osteoporosis therapy.

To determine the proportion of postmenopausal Thai women who would be classified as having high risk of fracture and eligible for anti-osteoporosis therapy according to the National Osteoporosis Foundation (NOF) criteria. Postmenopausal Thai women aged 40-90 years who had been screened for osteoporosis during 2014-2019 were recruited. Demographic data and osteoporosis risk factors were collected based on the Fracture Risk Assessment Tool (FRAX) questionnaire. Bone mineral density (BMD) at the femoral neck and lumbar spine measured using dual energy X-ray absorptiometry. Ten-year probabilities of hip and major osteoporotic fracture (MOF) were calculated based on the Thai FRAX model with BMD. The study's protocol was approved by the Institutional Ethical Committee (HE581241). A total of 3,280 postmenopausal women were included. The mean ± SD age was 63.6 ± 10.1 years. A total of 170 (5.2%) participants had a history of hip and/or vertebral fracture. After excluding these participants with fracture history, 699 (21.3%) had osteoporosis, 355 (10.8%) had osteopenia with high risk of fracture (FRAX 10-year probability of hip fracture ≥ 3% and/or MOF ≥ 20%), 1192 (36.3%) had osteopenia with low risk of fracture (FRAX 10-year probability of hip fracture < 3% and MOF < 20%) and 864 (26.3%) had normal BMD. Taken together, a total of 1,224 (37.3%) participants would be eligible for anti-osteoporosis therapy (prior fracture, osteoporosis or osteopenia with high risk of fracture). The prevalence of Thai postmenopausal women who would be eligible for anti-osteoporosis therapy was 37.3%.

Resting heart rate, self-reported physical activity in middle age, and long-term risk of hip fracture. A NOREPOS cohort study of 367,386 men and women.

Enhanced knowledge regarding modifiable risk factors for hip fractures are warranted. We aimed to study the associations between two indicators of physical fitness (resting heart rate and level of physical activity) in middle-aged individuals, and the risk of hip fractures during the subsequent three decades. Data on objectively measured resting heart rate and self-reported leisure time physical activity from a national health survey (1985-1999) was linked to a database including all hip fractures treated in Norwegian hospitals from 1994 through 2018. We calculated hazard ratios (HR) with 95% confidence intervals (95% CI) for hip fractures according to categories of resting heart rate (mean of two repeated measures), and leisure time physical activity level in adjusted Cox proportional hazard models. In total, 367,386 persons (52% women) aged 40 to 45years were included, of whom 5482 persons sustained a hip fracture during a mean follow-up of 24.8years. Higher resting heart rate was associated with higher hip fracture risk. Men with a resting heart rate above 80bpm, who also reported low levels of physical activity, had a HR of 1.82 (95% CI 1.49-2.22) for hip fracture compared to men with a resting heart rate below 70bpm who reported high levels of physical activity. The same measure of association for women was 1.62 (95% CI 1.28-2.06). Physical fitness measured by low resting heart rate in middle age, and a high physical activity level were associated with a lower long-term risk of hip fractures in both men and women.

Aging and Bone Metabolism.

Changes in bone architecture and metabolism with aging increase the likelihood of osteoporosis and fracture. Age-onset osteoporosis is multifactorial, with contributory extrinsic and intrinsic factors including certain medical problems, specific prescription drugs, estrogen loss, secondary hyperparathyroidism, microenvironmental and cellular alterations in bone tissue, and mechanical unloading or immobilization. At the histological level, there are changes in trabecular and cortical bone as well as marrow cellularity, lineage switching of mesenchymal stem cells to an adipogenic fate, inadequate transduction of signals during skeletal loading, and predisposition toward senescent cell accumulation with production of a senescence-associated secretory phenotype. Cumulatively, these changes result in bone remodeling abnormalities that over time cause net bone loss typically seen in older adults. Age-related osteoporosis is a geriatric syndrome due to the multiple etiologies that converge upon the skeleton to produce the ultimate phenotypic changes that manifest as bone fragility. Bone tissue is dynamic but with tendencies toward poor osteoblastic bone formation and relative osteoclastic bone resorption with aging. Interactions with other aging physiologic systems, such as muscle, may also confer detrimental effects on the aging skeleton. Conversely, individuals who maintain their BMD experience a lower risk of fractures, disability, and mortality, suggesting that this phenotype may be a marker of successful aging. © 2023 American Physiological Society. Compr Physiol 13:4355-4386, 2023.

Risk of fracture in adults with type 2 diabetes in Sweden: A national cohort study.

Type 2 diabetes mellitus (T2DM) is considered a risk factor for fracture but the evidence regarding the impact of T2DM on fracture risk is conflicting. The objective of the study was to determine if patients with T2DM have increased fracture risk and if T2DM-related risk factors could be identified. In this national cohort study in Sweden, we investigated the risk of fracture in 580,127 T2DM patients, identified through the national diabetes register including from both primary care and hospitals, and an equal number of population-based controls without diabetes matched for age, sex, and county from 2007 to 2017. The mean age at entry was 66.7 years and 43.6% were women. During a median follow-up time of 6.6 (interquartile range (IQR) 3.1 to 9.8) years, patients with T2DM had a marginally but significantly increased risk of major osteoporotic fracture (MOF) (hazard ratio (HR) 1.01 (95% confidence interval [CI] 1.00 to 1.03)) and hip fracture (HR 1.06 (95% CI 1.04 to 1.08)) compared to controls, associations that were only minimally affected (HR 1.05 (95% CI 1.03 to 1.06) and HR 1.11 (95% CI 1.09 to 1.14), respectively) by multivariable adjustment (age, sex, marital status, and an additional 20 variables related to general morbidity, cardiovascular status, risk of falls, and fracture). In a multivariable-adjusted Cox model, the proportion of the risk for all fracture outcomes (Heller's R2) explained by T2DM was below 0.1%. Among the T2DM patients, important risk factors for fracture were a low BMI (<25 kg/m2), long diabetes duration (≥15 years), insulin treatment, and low physical activity. In total, 55% of the T2DM patients had none of these risk factors and a significantly lower fracture risk than their respective controls. The relatively short mean duration of T2DM and lack of bone density data, constitute limitations of the analysis. In this study, we observed only a marginally increased fracture risk in T2DM, a condition that explained less than 0.1% of the fracture risk. Consideration of the herein identified T2DM-related risk factors could be used to stratify T2DM patients according to fracture risk.

Statin use in patients with type 2 diabetes has lower risk of hip fractures: A Taiwan national population-based study.

Type 2 diabetes mellitus (T2DM) frequently co-exists with osteoporosis and dyslipidemia. Statins have been commonly used in the treatment of dyslipidemia. Recent studies have indicated a therapeutic role of statins in decreasing the risk of osteoporosis and fractures, but conflicting results have been reported. This study investigated the association between statin use and hip fracture (HFx) risk among T2DM patients. A retrospective Taiwan population-based propensity-matched cohort study was performed using the Diabetes Mellitus Health Database from Taiwan National Health Insurance Research Database. Patients with newly diagnosed with T2DM between 2010 and 2014 were identified. Patients who previously used statins and had ever suffered HFx before the index date were excluded. HFx that occurred from 2010 to 2019 was collected to compute the cumulative rate of HFx. Hazard ratios (HRs) were calculated for the HFx risk according to the use or non-use of statins. To evaluate the dose-effect relationship of statins, sensitivity analyses were conducted. After propensity score matching for age and sex, 188,588 patients were identified as statin users and non-statin users. Statin use after T2DM diagnosis was associated with a decreased HFx risk with an adjusted HR (aHR) of 0.69 (P<0.001). A dose-effect relationship was identified. The aHRs for developing HFx were 1.29, 0.67, and 0.36 for patients who used 28-174, 175-447, and >447 cumulative defined daily doses of statins, respectively (P<0.001). Statin use in adults with T2DM showed a lower risk of HFx by demonstrating a dose-response relationship.

Association of Body Mass Index and Fracture Risk Varied by Affected Bones in Patients with Diabetes: A Nationwide Cohort Study.

Body mass index (BMI) is a risk factor for the type 2 diabetes (T2DM), and T2DM accompanies various complications, such as fractures. We investigated the effects of BMI and T2DM on fracture risk and analyzed whether the association varied with fracture locations. This study is a nationwide population-based cohort study that included all people with T2DM (n=2,746,078) who received the National Screening Program during 2009-2012. According to the anatomical location of the fracture, the incidence rate and hazard ratio (HR) were analyzed by dividing it into four categories: vertebra, hip, limbs, and total fracture. The total fracture had higher HR in the underweight group (HR, 1.268; 95% CI, 1.228 to 1.309) and lower HR in the obese group (HR, 0.891; 95% CI, 0.882 to 0.901) and the morbidly obese group (HR, 0.873; 95% CI, 0.857 to 0.89), compared to reference (normal BMI group). Similar trends were observed for HR of vertebra fracture. The risk of hip fracture was most prominent, the risk of hip fracture increased in the underweight group (HR, 1.896; 95% CI, 1.178 to 2.021) and decreased in the obesity (HR, 0.643; 95% CI, 0.624 to 0.663) and morbidly obesity group (HR, 0.627; 95% CI, 0.591 to 0.665). Lastly, fracture risk was least affected by BMI for limbs. In T2DM patients, underweight tends to increase fracture risk, and overweight tends to lower fracture risk, but association between BMI and fracture risk varied depending on the affected bone lesions.

Carrot and carotene and multiple health outcomes: an umbrella review of the evidence.

In recent years, the benefits of carrots and carotene in different areas of health have been examined. The purpose of this umbrella review was to identify the associations between carrots and carotene and multiple health outcomes. The review considered evidence from meta-analyses of interventional and observational studies of carrots and carotene and any health outcome. We comprehensively searched Web of Science, PubMed, and Embase. For each association, we estimated the summary effect size using random and fixed effects models and the 95% confidence interval. A total of 1329 studies were searched, and 30 meta-analyses with 26 health outcomes were identified that met the eligibility criteria. Carrot intake was associated with a lower risk of multiple cancer outcomes including breast cancer, lung cancer, pancreatic cancer, gastric cancer, urothelial cancer, and prostate cancer. Carotene intake was associated with a lower risk of fracture, age-related cataract, sunburn, Alzheimer's disease, breast cancer, lung cancer, pancreatic cancer, gastric cancer, esophageal cancer, prostate cancer, and head and neck cancer (HNC). Serum carotene was inversely associated with all-cause mortality, breast cancer, and lung cancer. Our study revealed that carrot or carotene intake could reduce the risk of various negative health outcomes. © 2023 Society of Chemical Industry.

Postmenopausal Osteoporosis and Osteopenia Management with a Combination of Once-Monthly Oral Ibandronate and Cholecalciferol—A Systematic Review

Postmenopausal osteoporosis and osteopenia are chronic and uncurable conditions that invariably lead to an increased risk of vertebral, hip, and femoral neck fracture if left untreated. Clinical guidelines establish, in general, pharmacological combinations allied to lifestyle changes as the mainstay of their management, and also increasing bone marrow density, lowering fracture risk, and improving quality of life are their main therapeutic goals. The objective of this systematic review was to analyze the available data in the scientific medical literature regarding the role of the ibandronate and cholecalciferol combination in postmenopausal osteoporosis and osteopenia management. Based on our results, we concluded that the above combination is safe and feasible for the clinical control of both conditions.

Real-world effectiveness of anti-osteoporosis medications for the prevention of incident hip and clinical vertebral fractures in patients on long-term glucocorticoid therapy: A nationwide health insurance claims database study in Japan.

Early initiation of anti-osteoporosis medications (AOMs) is recommended for patients on long-term glucocorticoid (GC) therapy. This study aimed to clarify the real-world effectiveness of AOMs against incident hip and vertebral fractures in patients undergoing GC therapy using the nationwide health insurance claims database of Japan (NDBJ). Patients aged ≥50years who were prescribed GC (≥5mg/day prednisolone or equivalent) for ≥90days and who were followed up regarding AOM prescription and hip and clinical vertebral fracture incidences for the subsequent 1080days between 2012 and 2018 were selected from NDBJ. Associations of AOMs prescribed within 90days since GC therapy initiation with hip or vertebral fracture risk were evaluated by Cox proportional hazards regression using propensity score inverse probability weighting (IPW) for receiving any AOM or individual AOMs. In total, 96,475 women and 98,385 men were included in the analysis; 38.0% of women and 27.6% of men received AOMs. Patients who received any AOM and those who received bisphosphonates or denosumab had a significantly lower risk of hip and clinical vertebral fractures than those who received no AOM in both sexes after propensity score IPW. Teriparatide was associated with an increased risk of both fractures in women and an increased risk of clinical vertebral fractures in men. Selection biases such as confounding by indication might have caused an underestimation of AOMs' protective effects. Bisphosphonates and denosumab were associated with a lower fracture incidence in patients on long-term GC therapy in real-world settings.

Medication holidays in osteoporosis: evidence-based recommendations from the Italian guidelines on 'Diagnosis, risk stratification, and continuity of care of fragility fractures' based on a systematic literature review.

Noncommunicable, chronic diseases need pharmacological interventions for long periods or even throughout life. The temporary or permanent cessation of medication for a specific period, known as a 'medication holiday,' should be planned by healthcare professionals. We evaluated the association between continuity (adherence or persistence) of treatment and several outcomes in patients with fragility fractures in the context of the development of the Italian Guidelines. Systematic review. We systematically searched PubMed, Embase, and the Cochrane Library up to November 2020 for randomized clinical trials (RCTs) and observational studies that analyzed medication holidays in patients with fragility fracture. Three authors independently extracted data and appraised the risk of bias of the included studies. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation methodology. Effect sizes were pooled in a meta-analysis using random effects models. Primary outcomes were refracture and quality of life; secondary outcomes were mortality and treatment-related adverse events. Six RCTs and nine observational studies met our inclusion criteria, ranging from very low to moderate quality. The adherence to antiosteoporotic drugs was associated with a lower risk of nonvertebral fracture [relative risk (RR) 0.42, 95% confidence interval (CI) 0.20-0.87; three studies] than nonadherence, whereas no difference was detected in the health-related quality of life. A reduction in refracture risk was observed when continuous treatment was compared to discontinuous therapy (RR 0.49, 95% CI 0.25-0.98; three studies). A lower mortality rate was detected for the adherence and persistence measures, while no significant differences were noted in gastrointestinal side effects in individuals undergoing continuous versus discontinuous treatment. Our findings suggest that clinicians should promote adherence and persistence to antiosteoporotic treatment in patients with fragility fractures unless serious adverse effects occur.