Risk Of Clinical Vertebral Fractures Research Articles

Average daily glucocorticoid dose, number of prescription days, and cumulative dose in the initial 90days of glucocorticoid therapy are associated with subsequent hip and clinical vertebral fracture risk: a retrospective cohort study using a nationwide health insurance claims database in Japan.

Fracture risk assessment is recommended at three months after glucocorticoid (GC) therapy initiation. This study aimed to assess whether GC exposure in the initial 90days of GC therapy is associated with subsequent hip and clinical vertebral fracture risk using the nationwide health insurance claims database of Japan (NDBJ). Patients aged 50years who were prescribed GC (≥ 70mg prednisolone or equivalent; PSL) in the initial 90days of GC therapy and were followed for hip and clinical vertebral fracture incidences for the subsequent 1080days were selected from NDBJ. Associations of GC exposure with hip or clinical vertebral fracture risk were evaluated by Cox regression analysis adjusted for potential confounders. We selected 316,396 women and 299,871 men for the GC-exposed group and 43,164 women and 33,702 men for the reference group. Higher GC doses and longer prescription days in the initial 90days of GC therapy were significantly and dose-dependently associated with increased fracture risk relative to the reference group. Patients receiving GC 5mg PSL/day had a significantly increased fracture risk in the stratum of 30-59days of GC prescription. In addition, female patients who received GC (≥ 1 and < 2.5mg PSL/day) for 90days in the initial 90days of GC therapy had a significantly increased fracture risk. GC exposure in the initial 90days of GC therapy was dose-dependently associated with hip and clinical vertebral fracture risk. GC may increase fracture risk with lower doses for shorter durations than previously reported. Fracture risk assessment three months after glucocorticoid (GC) therapy initiation is recommended. We found that GC exposure in the initial 90days of GC therapy at lower daily doses for shorter durations than previously reported were significantly and dose-dependently associated with fracture risk using a nationwide health insurance claims database.

Screening for the primary prevention of fragility fractures among adults aged 40 years and older in primary care: systematic reviews of the effects and acceptability of screening and treatment, and the accuracy of risk prediction tools

Screening for the primary prevention of fragility fractures among adults aged 40 years and older in primary care: systematic reviews of the effects and acceptability of screening and treatment, and the accuracy of risk prediction tools

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.

Adherence of bisphosphonate and decreased risk of clinical vertebral fracture in osteoporotic patients: A propensity score matching analysis

ObjectivesBisphosphonate is associated with a decreased risk of vertebral fractures due to osteoporosis. However, there are limited studies on how poor compliance with bisphosphonate affects the risk of vertebral fractures in a nationwide cohort. We aim to evaluate whether adherence to bisphosphonate affects the risk of fracture in osteoporosis patients. MethodsWe used the data of the Korean National Health Insurance Service Senior Cohort. A total of 33,315 (medication possession ratio [MPR]: 50) osteoporosis patients were matched using the propensity score matching method: those who received low-dose bisphosphonate and those who received high-dose bisphosphonate. Twenty-two confounding variables, including age, socioeconomic status, medications prescribed, and underlying diseases that may affect the risk of fracture were adjusted for propensity score matching. The risk of vertebral fracture was assessed by Cox proportional hazards regression. ResultsPatients with a higher MPR showed a decreased vertebral fracture risk than those with a lower MPR (MPR 50 = hazard ratio [HR] 0.909; 95% confidence interval [CI] 0.877–0.942 P < 0.001; MPR 70 = HR: 0.874, 95% CI: 0.838–0.913, P < 0.001; MPR 90 = HR: 0.822, 95% CI: 0.780–0.866, P < 0.001). MPR was associated with a decreased vertebral fracture risk in both groups with or without history of fracture. In the subgroup analysis, MPR was associated with a decreased vertebral fracture risk in women, in all ages, with or without T2DM, and with or without hypertension. ConclusionsHigher MPR is associated with a lower vertebral fracture risk.

Low-dose oral glucocorticoid therapy and risk of osteoporotic fractures in patients with rheumatoid arthritis: a cohort study using the Clinical Practice Research Datalink.

ObjectivesClinical trials have shown that low-dose glucocorticoid therapy in patients with RA reduces bone loss in hands or hip, but the effect on osteoporotic fractures is not yet clear. Therefore, we investigated the use of low-dose oral glucocorticoids and risk of osteoporotic fractures among patients with RA.MethodsThis was a cohort study including patients with RA aged 50+ years from the Clinical Practice Research Datalink between 1997 and 2017. Exposure to oral glucocorticoids was stratified by the most recent prescription in current (<6 months), recent (7–12 months) and past (>1 year) use, and average daily and cumulative doses. Risk of incident osteoporotic fractures (including hip, vertebrae, humerus, forearm, pelvis and ribs) was estimated by time-dependent Cox proportional-hazards models, adjusted for lifestyle parameters, comorbidities and comedications. Secondary analyses assessed osteoporotic fracture risk with a combination of average daily and cumulative doses of oral glucocorticoids.ResultsAmong 15 123 patients with RA (mean age 68.8 years, 68% females), 1640 osteoporotic fractures occurred. Current low-dose oral glucocorticoid therapy (≤7.5 mg prednisolone equivalent dose/day) in patients with RA was not associated with overall risk of osteoporotic fractures (adjusted hazard ratio 1.14, 95% CI 0.98, 1.33) compared with past glucocorticoid use, but was associated with an increased risk of clinical vertebral fracture (adjusted hazard ratio 1.59, 95% CI 1.11, 2.29). Results remained unchanged regardless of a short-term or a long-term use of oral glucocorticoids.ConclusionClinicians should be aware that even in RA patients who receive low daily glucocorticoid doses, the risk of clinical vertebral fracture is increased.

Effect of Dietary Protein Intake on Bone Mineral Density and Fracture Incidence in Older Adults in the Health, Aging, and Body Composition Study.

Dietary recommendations may underestimate the protein older adults need for optimal bone health. This study sought to determine associations of protein intake with bone mineral density (BMD) and fracture among community-dwelling White and Black older adults. Protein as a percentage of total energy intake (TEI) was assessed with a Food Frequency Questionnaire in 2160 older adults (73.5 ± 2.8 years; 51.5% women; 35.8% Black) in the Health, Aging, and Body Composition prospective cohort. Hip, femoral neck, and whole body BMD was assessed by dual-energy x-ray absorptiometry at baseline and 4 years, and lumbar trabecular, cortical, and integral BMD was assessed by computed tomography at baseline and 5 years. Fragility fractures over 5 years were adjudicated from self-report data collected every 6 months. Associations with tertiles of protein intake were assessed using analysis of covariance for BMD and multivariate Cox regression for fracture, adjusting for confounders. Participants in the upper protein tertile (≥15% TEI) had 1.8%-6.0% higher mean hip and lumbar spine BMD compared to the lower protein tertile (<13% TEI; p < .05). Protein intake did not affect change in BMD at any site over the follow-up period. Participants in the upper protein tertile had a reduced risk of clinical vertebral fracture over 5 years of follow-up (hazard ratio: 0.36 [95% confidence interval: 0.14, 0.97] vs lower protein tertile, p = .04). Older adults with higher protein intake (≥15% TEI) had higher BMD at the hip, whole body, and lumbar spine, and a lower risk of vertebral fracture.

Which is the preferred site for bone mineral density monitoring as an indicator of treatment-related anti-fracture effect in routine clinical practice? A registry-based cohort study.

The role of monitoring bone mineral density (BMD) as an indicator of an anti-fracture effect is controversial. Discordance between the spine and hip BMD is common and creates uncertainty in clinical practice. Using a population-based BMD Registry for the Province of Manitoba, Canada, we compared change in the spine and hip BMD as an indicator of treatment-related fracture risk reduction. The study cohort included 6093 women age >40years initiating osteoporosis treatment with two consecutive dual-energy X-ray absorptiometry (DXA) scans (mean interval 4.7years). We computed change in the spine, total hip, and femur neck BMD between the first and second DXA scans as categorical (categorized as stable, detectable decrease, or detectable increase) and continuous measures. We modeled time to first incident fracture, ascertained from health services data, using Cox regression adjusted for baseline fracture probability. During a mean follow-up of 12.1years, 995 women developed incident major osteoporotic fractures (MOF) including 246 with hip fractures and 301 with clinical vertebral fractures. Women with a detectable decrease in total hip BMD compared with stable BMD experienced an increase in MOF (adjusted hazard ratio [aHR] 1.46, 95% confidence interval [CI] 1.25-1.70) while those with a detectable increase in total hip BMD experienced a decrease in MOF (aHR 0.71, 95% CI 0.61-0.83), and these results were not attenuated when adjusted for change in spine BMD. Similar results were seen for hip and clinical vertebral fracture outcomes, when BMD change was assessed as a continuous measure, and when femur neck BMD monitoring was used instead of total hip BMD monitoring. Treatment-related increases in total hip BMD are associated with lower MOF, hip, and clinical vertebral fracture risk compared with stable BMD, while BMD decreases are associated with higher fracture risk. In contrast, spine BMD change is not independently associated with fracture risk.

A systematic review and meta-analysis of the effect of bisphosphonate drug holidays on bone mineral density and osteoporotic fracture risk.

We performed a systematic review and meta-analysis on the effect of drug holidays (discontinuation) on BMD and fracture risk. We searched PubMed, Embase, and Cochrane Library databases to locate controlled clinical trials and cohort studies evaluating the effect of drug holidays/discontinuation versus osteoporosis treatment continuation. We performed random-effects meta-analyses of hazard ratios of hip and any clinical osteoporotic fracture for individuals who discontinued bisphosphonates compared to persistent users. Thirteen records reporting results from eight different studies met inclusion criteria. The FLEX study found a reduced clinical vertebral fracture risk with 10years of alendronate therapy compared to 5 (RR 0.45, 95% CI 0.24-0.85), and the HORIZON extension studies found a reduced risk of morphometric vertebral fracture with 6years of zoledronic acid therapy compared to 3 (OR = 0.51, 95% CI 0.26-0.95); subgroup analyses showed that women with low hip BMD T-scores after the initial treatment period benefitted from continued treatment in terms of reduced vertebral fracture risk. Meta-analysis of adjusted hazard ratios of hip and any clinical osteoporotic fracture for women who discontinued bisphosphonates revealed no significant differences in the risk of hip fracture (summary estimate of HR 1.09, 95% CI 0.87-1.37) or any clinical fracture (summary estimate of HR 1.13, 95% CI 0.75-1.70) compared to persistent users. Bisphosphonate discontinuation may be considered for women who do not have low hip BMD after 3 to 5years of initial treatment, while women who have low hip BMD may benefit from treatment continuation.

Diuretic Use and Risk of Vertebral Fracture in Women

BackgroundVertebral fracture is the most common type of osteoporotic fracture. While thiazide diuretics, which are commonly prescribed for the treatment of hypertension, decrease calciuria, they may also induce hyponatremia, which has been associated with increased vertebral fracture risk. Loop diuretics increase calciuria, which would reduce bone mineral density and increase vertebral fracture risk, but they rarely cause hyponatremia. Recent studies on diuretics and fractures did not include or specifically examine vertebral fracture. The few studies of diuretics and vertebral fracture have been limited by cases defined by self-report or administrative data, relatively small number of cases, study design that was not prospective, and lack of long-term follow-up with updated information on diuretic use. MethodsWe conducted a prospective cohort study of thiazide diuretic use, loop diuretic use, and risk of incident clinical vertebral fracture in 55,780 women, 55-82 years of age, participating in the Nurses' Health Study, without a prior history of any fracture. Diuretic use was assessed by questionnaire every 4 years. Self-reported vertebral fracture was confirmed by medical record review. Cox proportional-hazards models were used to simultaneously adjust for potential confounders. ResultsOur analysis included 420 incident vertebral fracture cases documented between 2002 and 2012. The multivariate-adjusted relative risk of clinical vertebral fracture for women taking thiazides compared with women not taking thiazides was 1.47 (95% confidence interval, 1.18-1.85). The multivariate adjusted relative risk of vertebral fracture for women taking loop diuretics compared with women not taking loop diuretics was 1.59 (95% confidence interval, 1.12-2.25). ConclusionThiazide diuretics and loop diuretics are each independently associated with increased risk of vertebral fracture in women.

Novel Genetic Variants Associated With Increased Vertebral Volumetric BMD, Reduced Vertebral Fracture Risk, and Increased Expression of SLC1A3 and EPHB2.

Genome-wide association studies (GWASs) have revealed numerous loci for areal bone mineral density (aBMD). We completed the first GWAS meta-analysis (n = 15,275) of lumbar spine volumetric BMD (vBMD) measured by quantitative computed tomography (QCT), allowing for examination of the trabecular bone compartment. SNPs that were significantly associated with vBMD were also examined in two GWAS meta-analyses to determine associations with morphometric vertebral fracture (n = 21,701) and clinical vertebral fracture (n = 5893). Expression quantitative trait locus (eQTL) analyses of iliac crest biopsies were performed in 84 postmenopausal women, and murine osteoblast expression of genes implicated by eQTL or by proximity to vBMD-associated SNPs was examined. We identified significant vBMD associations with five loci, including: 1p36.12, containing WNT4 and ZBTB40; 8q24, containing TNFRSF11B; and 13q14, containing AKAP11 and TNFSF11. Two loci (5p13 and 1p36.12) also contained associations with radiographic and clinical vertebral fracture, respectively. In 5p13, rs2468531 (minor allele frequency [MAF] = 3%) was associated with higher vBMD (β = 0.22, p = 1.9 × 10-8 ) and decreased risk of radiographic vertebral fracture (odds ratio [OR] = 0.75; false discovery rate [FDR] p = 0.01). In 1p36.12, rs12742784 (MAF = 21%) was associated with higher vBMD (β = 0.09, p = 1.2 × 10-10 ) and decreased risk of clinical vertebral fracture (OR = 0.82; FDR p = 7.4 × 10-4 ). Both SNPs are noncoding and were associated with increased mRNA expression levels in human bone biopsies: rs2468531 with SLC1A3 (β = 0.28, FDR p = 0.01, involved in glutamate signaling and osteogenic response to mechanical loading) and rs12742784 with EPHB2 (β = 0.12, FDR p = 1.7 × 10-3 , functions in bone-related ephrin signaling). Both genes are expressed in murine osteoblasts. This is the first study to link SLC1A3 and EPHB2 to clinically relevant vertebral osteoporosis phenotypes. These results may help elucidate vertebral bone biology and novel approaches to reducing vertebral fracture incidence. © 2016 American Society for Bone and Mineral Research.

Risk of vertebral and non-vertebral fractures in patients with sarcoidosis: a population-based cohort.

SummaryIn this retrospective cohort study using the Clinical Practice Research Datalink (CPRD), patients with sarcoidosis have an increased risk of clinical vertebral fractures and when on recent treatment with oral glucocorticoids, also an increased risk of any fractures and osteoporotic fractures.IntroductionSarcoidosis is a chronic inflammatory disease, in which fragility fractures have been reported despite normal BMD. The aim of this study was to assess whether patients with sarcoidosis have an increased risk of clinical fractures compared to the general population.MethodsA retrospective cohort study was conducted using the CPRD. All patients with a CPRD code for sarcoidosis between January 1987 and September 2012 were included. Cox proportional hazards models were used to derive adjusted relative risks (RRs) of fractures in all sarcoidosis patients compared to matched controls, and within the sarcoidosis group according to use and dose of systemic glucocorticoids.ResultsFive thousand seven hundred twenty-two sarcoidosis patients (mean age 48.0 years, 51 % females, mean follow-up 6.7 years) were identified.Compared to 28,704 matched controls, the risk of any fracture was not different in patients with sarcoidosis. However, the risk of clinical vertebral fractures was significantly increased (adj RR 1.77; 95 % CI 1.06–2.96) and the risk of non-vertebral fractures was decreased although marginally significant (adj RR 0.87; 95 % CI 0.77–0.99). Compared to sarcoidosis patients not taking glucocorticoids, recent use of systemic glucocorticoids was associated with an increased risk of any fracture (adj RR 1.50; 95 % CI 1.20–1.89) and of an osteoporotic fracture (adj RR 1.47; 95 % CI 1.07–2.02).ConclusionsPatients with sarcoidosis have an increased risk of clinical vertebral fractures, and when using glucocorticoid therapy, an increased risk of any fractures and osteoporotic fractures. In contrast, the risk of non-vertebral fractures maybe decreased. Further investigation is needed to understand the underlying mechanisms of these contrasting effects on fracture risk.

High Serum SHBG Predicts Incident Vertebral Fractures in Elderly Men.

ABSTRACTPrevious prospective cohort studies have shown that serum levels of sex steroids and sex hormone‐binding globulin (SHBG) associate with nonvertebral fracture risk in men. The predictive value of sex hormones and SHBG for vertebral fracture risk specifically is, however, less studied. Elderly men (aged ≥65 years) from Sweden and Hong Kong participating in the Osteoporotic Fractures in Men (MrOS) study had baseline estradiol and testosterone analyzed by gas chromatography–mass spectrometry (GC‐MS) and SHBG by immunoradiometric assay (IRMA). Incident clinical vertebral fractures (n = 242 cases) were evaluated in 4324 men during an average follow‐up of 9.1 years. In a subsample of these men (n = 2256), spine X‐rays were obtained at baseline and after an average follow‐up of 4.3 years to identify incident radiographic vertebral fractures (n = 157 cases). The likelihood of incident clinical and radiographic vertebral fractures was estimated by Cox proportional hazards models and logistic regression models, respectively. Neither serum estradiol (hazard ratio [HR] per SD increase = 0.93, 95% confidence interval [CI] 0.80–1.08) nor testosterone (1.05, 0.91–1.21) predicted incident clinical vertebral fractures in age‐adjusted models in the combined data set. High serum SHBG, however, associated with increased clinical vertebral fracture risk (1.24, 1.12–1.37). This association remained significant after further adjustment for FRAX with or without bone mineral density (BMD). SHBG also associated with increased incident radiographic vertebral fracture risk (combined data set; odds ratio [OR] per SD increase = 1.23, 95% CI 1.05–1.44). This association remained significant after adjustment for FRAX with or without BMD. In conclusion, high SHBG predicts incident clinical and radiographic vertebral fractures in elderly men and adds moderate information beyond FRAX with BMD for vertebral fracture risk prediction. © 2015 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

How long do you continue bisphosphonate therapy for osteoporosis?

Evidence-Based Answer At 10-year follow-up, patients who stopped bisphosphonates after 5 years have similar nonvertebral fracture rates as patients who remain on bisphosphonates for a 10 full years; however, they have greater changes in bone mineral density (BMD) and their risk of clinical vertebral fractures may be higher (SOR: B, large RCT). Patients who take bisphosphonates for 3 years will have a decrease in BMD after discontinuation for 1 year, but their mean BMD will still be higher than before bisphosphonate therapy was started (SOR: C, diseaseoriented outcome).

Treatment holidays in patients with postmenopausal osteoporosis: Whom and when?

The controversy about the ideal duration of treatment with bisphosphonates is not new. As early as in 2005, some experts suggested that treatment with alendronate for patients with postmenopausal osteoporosis could be discontinued after five years, provided no fractures had occurred during this period and bone mass had improved as compared to baseline. This recommendation was based on the lack of data showing an additional fracture rate reduction when treatment was continued beyond five years, and on the fact that remodeling markers continued to be suppressed despite treatment discontinuation, which suggested a residual effect. The final data of the FLEX study were reported in 2006. In this study, 1099 women from the Fracture Intervention Trial (conducted to assess the anti-fracture efficacy of alendronate) were randomized again to three treatment arms: placebo, alendronate 5 mg/day, and alendronate 10 mg/day, for five years. In the placebo group, a decrease in bone mineral density (BMD) associated with increased remodeling was seen, but values prior to the start of treatment were not reached. The patients who continued to receive alendronate had a lower risk of clinical vertebral fractures as compared to the placebo patients, but no differences

Epidemiology of osteoporosis and fractures in ankylosing spondylitis

Osteoporosis and fractures, especially vertebral fractures, are a frequent complication of ankylosing spondylitis, even in the early stages of the disease. The risk of osteoporosis appears to be associated with elevated biochemical markers of bone turnover, increased pro-inflammatory cytokines, lower BMD, lower body weight and longer disease duration. Using the WHO criteria (T score < -2.5), the prevalence of osteoporosis determined by BMD is about 29% in the spine and 12% in the hip in patients with ankylosing spondylitis, which compares with 2% and 1% respectively for controls. Although BMD is generally lower in patients with early disease, with progressive disease, the spine site becomes much less reliable due to the presence of syndesmophytes and periosteal new bone formation. In advanced cases, DXA becomes less reliable but using QCT, bone loss can be shown to continue within the vertebra and hips as well as an increase in cortical BMD and width. The epidemiology of fractures in ankylosing spondylitis remains unclear although vertebral fractures have been most studied. The risk of clinical vertebral fractures is significantly increased (OR approximately 7.7 95% CI 4.3-12.6) and the cumulative incidence of clinical vertebral fractures is higher in men (OR 10.7 versus 4.2 in women) and increased especially during the first 5 years of the disease. The prevalence and incidence of non-vertebral fractures has been less well studied but in most reports appears to be about the same as in the control population. Managing skeletal complications in anklosing spondylitis should include DXA of the spine and hip early in the disease. In more advanced disease, spinal DXA is not a useful predictor of fracture. In these circumstances, QCT should be considered. If a vertebral fracture is suspected, spinal imaging is required in order to avoid delays in diagnosis and therapy.

Denosumab for the prevention of osteoporotic fractures in postmenopausal women

This paper presents a summary of the evidence review group (ERG) report into denosumab for the prevention of osteoporotic fractures in postmenopausal women. Denosumab has been shown in a large randomised trial to reduce the frequency of osteoporotic fractures when given subcutaneously at 6-monthly intervals. Compared with placebo, the relative risks of clinical vertebral and hip fractures were 0.32 and 0.60, respectively. Clinical vertebral fractures occurred in 0.8% of women taking denosumab and 2.6% of control subjects. Hip fractures occurred in 1.2% of women on placebo and 0.7% on denosumab. The expected use is in women who cannot tolerate oral bisphosphonates. Other options in that situation include strontium ranelate and zoledronate, which, compared with placebo, also reduced the risk of clinical vertebral fractures [relative risk (RR) 0.65 and 0.23, respectively]. Zoledronate also significantly reduced the risk of hip fractures (RR 0.59). The ERG concluded that zoledronate was the main comparator. The relative cost-effectiveness of denosumab and zoledronate depends mainly on assumptions about costs of administration.

Denosumab for the prevention of osteoporotic fractures in postmenopausal women

This paper presents a summary of the evidence review group (ERG) report into denosumab for the prevention of osteoporotic fractures in postmenopausal women. Denosumab has been shown in a large randomised trial to reduce the frequency of osteoporotic fractures when given subcutaneously at 6-monthly intervals. Compared with placebo, the relative risks of clinical vertebral and hip fractures were 0.32 and 0.60, respectively. Clinical vertebral fractures occurred in 0.8% of women taking denosumab and 2.6% of control subjects. Hip fractures occurred in 1.2% of women on placebo and 0.7% on denosumab. The expected use is in women who cannot tolerate oral bisphosphonates. Other options in that situation include strontium ranelate and zoledronate, which, compared with placebo, also reduced the risk of clinical vertebral fractures [relative risk (RR) 0.65 and 0.23, respectively]. Zoledronate also significantly reduced the risk of hip fractures (RR 0.59). The ERG concluded that zoledronate was the main comparator. The relative cost-effectiveness of denosumab and zoledronate depends mainly on assumptions about costs of administration.

Ethnic difference of clinical vertebral fracture risk

SummaryVertebral fractures are the most common osteoporotic fractures. Data on the vertebral fracture risk in Asia remain sparse. This study observed that Hong Kong Chinese and Japanese populations have a less dramatic increase in hip fracture rates associated with age than Caucasians, but the vertebral fracture rates were higher, resulting in a high vertebral-to-hip fracture ratio. As a result, estimation of the absolute fracture risk for Asians may need to be readjusted for the higher clinical vertebral fracture rate.IntroductionVertebral fractures are the most common osteoporotic fractures. Data on the vertebral fracture risk in Asia remain sparse. The aim of this study was to report the incidence of clinical vertebral fractures among the Chinese and to compare the vertebral-to-hip fracture risk to other ethnic groups.MethodsFour thousand, three hundred eighty-six community-dwelling Southern Chinese subjects (2,302 women and 1,810 men) aged 50 or above were recruited in the Hong Kong Osteoporosis Study since 1995. Baseline demographic characteristics and medical history were obtained. Subjects were followed annually for fracture outcomes with a structured questionnaire and verified by the computerized patient information system of the Hospital Authority of the Hong Kong Government. Only non-traumatic incident hip fractures and clinical vertebral fractures that received medical attention were included in the analysis. The incidence rates of clinical vertebral fractures and hip fractures were determined and compared to the published data of Swedish Caucasian and Japanese populations.ResultsThe mean age at baseline was 62 ± 8.2 years for women and 68 ± 10.3 years for men. The average duration of follow-up was 4.0 ± 2.8 (range, 1 to 14) years for a total of 14,733 person-years for the whole cohort. The incidence rate for vertebral fracture was 194/100,000 person-years in men and 508/100,000 person-years in women, respectively. For subjects above the age of 65, the clinical vertebral fracture and hip fracture rates were 299/100,000 and 332/100,000 person-years, respectively, in men, and 594/100,000 and 379/100,000 person-years, respectively, in women. Hong Kong Chinese and Japanese populations have a less dramatic increase in hip fracture rates associated with age than Caucasians. At the age of 65 or above, the hip fracture rates for Asian (Hong Kong Chinese and Japanese) men and women were less than half of that in Caucasians, but the vertebral fracture rate was higher in Asians, resulting in a high vertebral-to-hip fracture ratio.ConclusionsThe incidences of vertebral and hip fractures, as well as the vertebral-to-hip fracture ratios vary in Asians and Caucasians. Estimation of the absolute fracture risk for Asians may need to be readjusted for the higher clinical vertebral fracture rate.

Bone turnover markers and prediction of fracture: A prospective follow-up study of 1040 elderly women for a mean of 9 years

Osteoporosis is characterized by compromised bone mass and strength, predisposing to an increased risk of fracture. Increased bone metabolism has been suggested to be a risk factor for fracture. The aim of this study was to evaluate whether baseline bone turnover markers are associated with long-term incidence of fracture in a population-based sample of 1040 women who were 75 years old (Malmö OPRA study). Seven bone markers (S-TRACP5b, S-CTX-I, S-OC[1-49], S-TotalOC, S-cOC, S-boneALP, and urinary osteocalcin) were measured at baseline and 1-year follow-up visit. During the mean follow-up of 9.0 years (range 7.4-10.9), 363 women sustained at least one fracture of any type, including 116 hip fractures and 103 clinical vertebral fractures. High S-TRACP5b and S-CTX-I levels were associated with increased risk of any fracture with hazard ratios [HRs (95% confidence interval)] of 1.16 (1.04-1.29) and 1.13 (1.01-1.27) per SD increase, respectively. They also were associated with increased risk of clinical vertebral fracture with HRs of 1.22 (1.01-1.48) and 1.32 (1.05-1.67), respectively. Markers were not associated with risk for hip fracture. Results were similar when we used resorption markers, including urinary osteocalcin, measured at the 1-year visit or an average of the two measurements. The HRs were highest for any fracture in the beginning of the follow-up period, 2.5 years from baseline. For vertebral fractures, the association was more pronounced and lasted for a longer period of time, at least for 5 years. In conclusion, elevated levels of S-TRACP5b, S-CTX-I, and urinary osteocalcin are associated with increased fracture risk for up to a decade in elderly women.

Five-year and 10-year absolute risk of clinical vertebral fracture for individuals

Five-year and 10-year absolute risk of clinical vertebral fracture for individuals