Evaluation of urinary N-telopeptide of type I collagen measurements in the management of osteoporosis in clinical practice.
Baxter I, Rogers A, Eastell R, Peel N.
NIHR Musculoskeletal Biomedical Research Unit, Department of Human Metabolism, University of Sheffield, Sheffield, UK.
We measured urinary N-telopeptide of type I collagen (U-NTX) to monitor response to bisphosphonates for osteoporosis. Decrease in U-NTX was associated with increase in spine bone density. A lesser response in U-NTX was more likely in those with secondary osteoporosis or with poor compliance. U-NTX may be a useful early indicator of treatment non-compliance or secondary osteoporosis. INTRODUCTION: This study aims to determine the utility of the bone resorption marker, U-NTX, in the clinical setting, to monitor the response to bisphosphonate therapy (alendronate and risedronate) for osteoporosis. METHODS: A retrospective evaluation of data collected as part of the bone turnover marker monitoring service in the Metabolic Bone Centre, Sheffield, UK. Treatment compliance, underlying causes of osteoporosis, change in U-NTX/creatinine (Cr) at 4 months and change in spine and hip bone mineral density (BMD) by dual-energy X-ray absorptiometry were recorded. Treatment response was defined as either a change in U-NTX/Cr greater than a pre-defined least significant change (LSC) of 54 % or to within the lower half of a pre-defined pre-menopausal reference interval (≤30 nM BCE/mmol Cr). RESULTS: A greater decrease in U-NTX/Cr at 4 months was associated with a greater increase in spine BMD at 18 months (r = -0.33; P < 0.0001, Pearson's correlation). The mean U-NTX/Cr at 4 months was higher in patients with secondary osteoporosis compared with those with primary osteoporosis (P < 0.01, ANOVA). A lesser response in U-NTX/Cr increased the likelihood of secondary osteoporosis or poor treatment compliance (P = 0.04, Fisher's exact test). A lack of response in U-NTX/Cr to within the lower half of the reference interval was a better indicator of secondary osteoporosis and treatment non-compliance than a change in U-NTX/Cr greater than LSC. CONCLUSIONS: Treatment monitoring using U-NTX/Cr has a place in clinical practice for the early identification of non-compliance or presence of secondary osteoporosis.
Severity of aortic calcification is positively associated with vertebral fracture in older men-a densitometry study in the STRAMBO cohort.
Szulc P, Samelson EJ, Sornay-Rendu E, Chapurlat R, Kiel DP.
In older men, severe abdominal aortic calcification and vertebral fracture (both assessed using dual-energy X-ray absorptiometry) were positively associated after adjustment for confounders including bone mineral density. INTRODUCTION: Abdominal aortic calcification (AAC) is associated with higher fracture risk, independently of low bone mineral density (BMD). Dual-energy X-ray absorptiometry (DXA) can be used to assess both vertebral fracture and AAC and requires less time, cost, and radiation exposure. METHODS: We conducted a cross-sectional study of the association between AAC and prevalent vertebral fractures in 901 men ≥50 years old. We used DXA (vertebral fracture assessment) to evaluate BMD, vertebral fracture, and AAC. RESULTS: Prevalence of vertebral fracture was 11 %. Median AAC score was 1 and 12 % of men had AAC score >6. After adjustment for age, weight, femoral neck BMD, smoking, ischemic heart disease, diabetes, and hypertension, AAC score >6 (vs ≤6) was associated with 2.5 (95 % CI, 1.4-4.5) higher odds of vertebral fracture. Odds of vertebral fracture for AAC score >6 increased with vertebral fracture severity (grade 1, OR = 1.8; grade 2, OR = 2.4; grade 3, OR = 4.4; trend p < 0.01) and with the number of vertebral fractures (1 fracture, OR = 2.0, >1 fracture, OR = 3.5). Prevalence of vertebral fracture was twice as high in men having both a T-score < -2.0 and an AAC score > 6 compared with men having only one of these characteristics. CONCLUSIONS: Men with greater severity AAC had greater severity and greater number of vertebral fractures, independently of BMD and co-morbidities. DXA can be used to assess vertebral fracture and AAC. It can provide a rapid, safe, and less expensive alternative to radiography. DXA may be an important clinical tool to identify men at high risk of adverse outcomes from osteoporosis and cardiovascular disease.
The effect of proton pump inhibitors on fracture risk: report from the Canadian Multicenter Osteoporosis Study.
Fraser LA, Leslie WD, Targownik LE, Papaioannou A, Adachi JD; CaMos Research Group.
A large Canadian cohort was studied over 10 years to see if proton pump inhibitor (PPI) use increased the risk of sustaining a fragility fracture. We found an increased risk of fracture in individuals who used PPIs. The risk remained after controlling for other known fracture risk factors. INTRODUCTION: Multiple retrospective studies have linked proton pump inhibitor use with increased risk of fragility fracture. We prospectively studied the association between PPI use and fracture in a large cohort over a 10-year period while controlling for known fracture risk factors. METHODS: We studied 9,423 participants in the Canadian Multicenter Osteoporosis Study. The cohort was formed in 1995-1997 and followed for 10 years with monitoring for incident nontraumatic fracture and PPI use. Cox regression analyses were used to assess the association between PPI use and incident fracture risk. RESULTS: PPI use, coded as a time-dependent variable, was associated with a shorter time to first nontraumatic fracture, hazard ratio (HR) = 1.75 (95 % confidence interval (CI) 1.41-2.17, p < 0.001). After controlling for multiple risk factors, including femoral neck bone density, the association remained significant, HR = 1.40 (95 % CI 1.11-1.77, p = 0.004). Similar results were obtained after controlling for bisphosphonate use, using PPI "ever" use, or when the outcome was restricted to hip fracture. CONCLUSIONS: In this large prospective population-based cohort study, we found an association between PPI use and increased risk of fragility fracture. Although the increased risk found was modest, this finding is important, given the high prevalence of PPI use and the excess morbidity and mortality associated with osteoporosis-related fractures.
Quantitative ultrasound and fracture risk prediction in non-osteoporotic men and women as defined by WHO criteria.
Chan MY, Nguyen ND, Center JR, Eisman JA, Nguyen TV.
Osteoporosis and Bone Biology Program, Garvan Institute of Medical Research, 384 Victoria Street, Sydney, NSW, 2010, Australia.
This study sought to determine the association between calcaneal quantitative ultrasound (QUS) and fracture risk in individuals without osteoporosis according to the World Health Organization criteria (i.e., BMD T-score > -2.5). We found that calcaneal QUS is an independent predictor of fracture risk in women with non-osteoporotic bone mineral density (BMD). INTRODUCTION: More than 50 % of women and 70 % of men who sustain a fragility fracture have BMD above the osteoporotic threshold (T-score > -2.5). Calcaneal QUS is associated with fracture risk. This study aimed to test the hypothesis that low calcaneal QUS is associated with increased fracture risk in individuals with non-osteoporotic BMD.METHODS: We included 312 women and 390 men aged 62-90 years with BMD T-score > -2.5 at femoral neck. QUS was measured in broadband ultrasound attenuation (BUA) at the calcaneus using a CUBA sonometer. BMD was measured at the femoral neck (FNBMD) by dual energy X-ray absorptiometry using GE Lunar DPX-L densitometer. The incidences of any fragility fracture were ascertained by X-ray reports during the follow-up period from 1994 to 2011. RESULTS: Of the 702 participants, 26 % of women (n = 80/312) and 14 % of men (n = 53/390) experienced at least one fragility fracture during the follow-up period. In women, after adjusting for covariates, increased risk of any fracture was significantly associated with decreased BUA (HR = 1.50; 95 % CI, 1.13-1.99). Compared with that of FNBMD, the models with BUA, in women, had greater AUC (0.71, 0.85, 0.71 for any, hip and vertebral fracture, respectively), and yielded a net reclassification improvement of 16.4 % (P = 0.009) when combined with FNBMD. In men, BUA was not significantly associated with fracture risk before and after adjustment. CONCLUSION: These results suggest that calcaneal BUA is an independent predictor of fracture risk in women with non-osteoporotic BMD.
Cold-activated brown adipose tissue is an independent predictor of higher bone mineral density in women.
Lee P, Brychta RJ, Collins MT, Linderman J, Smith S, Herscovitch P, Millo C, Chen KY, Celi FS.
In animals, defective brown adipogenesis leads to bone loss. Whether brown adipose tissue (BAT) mass relates to bone mineral density (BMD) in humans is unclear. We determined the relationship between BAT mass and BMD by cold-stimulated positron-emission tomography (PET) and dual-energy X-ray absorptiometry (DXA) in healthy volunteers. Higher BAT mass was associated with higher BMD in healthy women, but not in men, independent of age and body composition. INTRODUCTION: Contrary to the traditional belief that BAT is present only in infants, recent studies revealed significant depots of BAT present in adult humans. In animals, defective brown adipogenesis leads to bone loss. While white adipose tissue mass is a known determinant of BMD in humans, the relationship between BAT and BMD in humans is unclear. We thus examined the relationship between BAT and BMD in healthy adults. METHODS: BAT volume (ml) and activity (standard uptake value) were determined by (18)F-fluorodeoxyglucose PET after overnight mild cold exposure at 19 °C, and BMD was determined by DXA. RESULTS: Among 24 healthy adults (age 28 ± 1 years, F = 10), BAT volumes were 82.4 ± 99.5 ml in women and 49.7 ± 54.5 ml in men. Women manifested significantly higher BAT activity, by 9.4 ± 8.1 % (p = 0.03), than men. BAT volume correlated positively with total and spine BMD (r (2) = 0.40 and 0.49, respectively, p < 0.02) in women and remained a significant predictor after adjustment for age, fat, and lean body mass (p < 0.05). Total and spine BMD were higher in women who harbored visually detectable BAT on PET images than those without by 11 ± 2 % (p = 0.02) and 22 ± 2 % (p < 0.01), respectively. No associations were observed between BAT parameters and BMD in men. CONCLUSIONS: This study demonstrated higher BMD among healthy women with more abundant BAT, independent of age and other body compositional parameters. This was not observed in men. The data suggest that brown adipogenesis may be physiologically related to modulation of bone density.