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Summary: The aim of this study was to examine the effects of bisphosphonate discontinuation on bone metabolism at the spine and hip measured using F-fluoride PET. Bone metabolism at the spine remained stable following discontinuation of alendronate and risedronate at 1 year but increased in the hip in the alendronate group only. Introduction: Bisphosphonates such as alendronate (ALN) or risedronate (RIS) have persistent effects on spine BMD following discontinuation. Methods: Positron emission tomography (PET) was used to examine regional bone metabolism in 20 postmenopausal women treated with ALN ( n = 11) or RIS ( n = 9) for a minimum of 3 years at screening (range 3-9 years, mean 5 years for both groups). Subjects underwent a dynamic scan of the lumbar spine and a static scan of both hips at baseline and 6 and 12 months following treatment discontinuation. F-fluoride plasma clearance (K) at the spine was calculated using a three-compartment model. Standardised uptake values (SUV) were calculated for the spine, total hip, femoral neck and femoral shaft. Measurements of BMD and biochemical markers of bone turnover were also performed. Results: With the exception of a significant decrease in spine BMD in the ALN group, BMD remained stable. Bone turnover markers increased significantly from baseline by 12 months for both study groups. Measurements of K and SUV at the spine and femoral neck did not change significantly in either group. SUV at the femoral shaft and total hip increased significantly but in the ALN group only, increasing by 33.8% ( p = 0.028) and 24.0% ( p = 0.013), respectively. Conclusions: Bone metabolism at the spine remained suppressed following treatment discontinuation. A significant increase in SUV at the femoral shaft and total hip after 12 months was observed but for the ALN group only. This study was small, and further clinical studies are required to fully evaluate the persistence of BP treatment. [ABSTRACT FROM AUTHOR]

Summary: High bone mineral density on routine dual energy X-ray absorptiometry (DXA) may indicate an underlying skeletal dysplasia. Two hundred fifty-eight individuals with unexplained high bone mass (HBM), 236 relatives (41% with HBM) and 58 spouses were studied. Cases could not float, had mandible enlargement, extra bone, broad frames, larger shoe sizes and increased body mass index (BMI). HBM cases may harbour an underlying genetic disorder. Introduction: High bone mineral density is a sporadic incidental finding on routine DXA scanning of apparently asymptomatic individuals. Such individuals may have an underlying skeletal dysplasia, as seen in LRP5 mutations. We aimed to characterize unexplained HBM and determine the potential for an underlying skeletal dysplasia. Methods: Two hundred fifty-eight individuals with unexplained HBM (defined as L1 Z-score ≥ +3.2 plus total hip Z-score ≥ +1.2, or total hip Z-score ≥ +3.2) were recruited from 15 UK centres, by screening 335,115 DXA scans. Unexplained HBM affected 0.181% of DXA scans. Next 236 relatives were recruited of whom 94 (41%) had HBM (defined as L1 Z-score + total hip Z-score ≥ +3.2). Fifty-eight spouses were also recruited together with the unaffected relatives as controls. Phenotypes of cases and controls, obtained from clinical assessment, were compared using random-effects linear and logistic regression models, clustered by family, adjusted for confounders, including age and sex. Results: Individuals with unexplained HBM had an excess of sinking when swimming (7.11 [3.65, 13.84], p < 0.001; adjusted odds ratio with 95% confidence interval shown), mandible enlargement (4.16 [2.34, 7.39], p < 0.001), extra bone at tendon/ligament insertions (2.07 [1.13, 3.78], p = 0.018) and broad frame (3.55 [2.12, 5.95], p < 0.001). HBM cases also had a larger shoe size (mean difference 0.4 [0.1, 0.7] UK sizes, p = 0.009) and increased BMI (mean difference 2.2 [1.3, 3.1] kg/m, p < 0.001). Conclusion: Individuals with unexplained HBM have an excess of clinical characteristics associated with skeletal dysplasia and their relatives are commonly affected, suggesting many may harbour an underlying genetic disorder affecting bone mass. [ABSTRACT FROM AUTHOR]

Summary: We examined the effect of weight and weight change on the long-term precision of spine and hip bone mineral density (BMD) in a group of 64 postmenopausal women studied over a 10-year period. Long-term precision errors were 50% larger than short-term errors. Over the range 50-90-kg weight was associated with a statistically significantly larger precision error when precision was expressed in BMD units, but not when expressed as the coefficient of variation (CV). Weight changes up to 5 kg had little effect on precision. Introduction: Reliable knowledge of the precision of bone mineral density (BMD) measurements is important for the interpretation of follow-up dual-energy X-ray absorptiometry (DXA) scans. In this study, we examined the effect of body weight and change in weight on the long-term precision of spine and hip BMD. Methods: The study population was a group of 64 postmenopausal women enrolled in a 16-year trial of tibolone. We analyzed the spine, femoral neck, and total hip BMD data acquired over a 10-year period on a Hologic QDR4500A densitometer using linear regression to examine the trend of BMD with time for each subject. Precision was expressed in BMD units (g cm) (standard error of the estimate, SEE) and also as the coefficient of variation (CV). Results: The long-term precision errors were in BMD (CV) units: 0.018 g cm (1.9%) for spine, 0.017 g cm (2.3%) for femoral neck, and 0.016 g cm (1.7%) for total hip BMD. An inverse relationship between CV and BMD was found for the spine ( P = 0.003) and total hip ( P = 0.043) sites, but none between SEE and BMD. For spine BMD, there were statistically significant correlations between SEE and weight ( P = 0.025) and body thickness ( P = 0.027). For femoral neck BMD, there were correlations between SEE and weight ( P = 0.030), body mass index (BMI) ( P = 0.023) and thickness ( P = 0.021), but no correlations for total hip BMD or when precision was expressed as the CV. When study subjects were grouped in quartiles according to weight, the spine BMD SEE increased from 0.014 g cm for women in the lowest quartile (46-62 kg) to 0.018 g cm for women in the highest quartile (80-105 kg) ( P = 0.008). There was a trend for SEE to be greater in individuals with larger weight changes, although these tended to be the heavier subjects. Conclusions: From the study, we were able to come up with the following conclusions: (1) long-term precision errors were 50% larger than short-term errors, (2) over the range 50 to 90 kg (BMI: 20-35 kg m), body weight had a small but statistically significant effect on precision expressed in BMD units, but not when expressed as the CV, and (3) weight changes up to 5 kg had little effect on precision. More studies of individuals >100 kg are required to fully investigate the dependence of DXA scan precision on weight. [ABSTRACT FROM AUTHOR]

Summary: We investigated the association between fibroblast growth factor-23 (FGF-23) and (1) the biochemical parameters implicated in chronic kidney disorder (CKD)-bone and mineral disorder (CKD-MBD) and (2) bone mineral density (BMD) in patients with CKD 1-4. C-reactive protein (CRP) and serum phosphate correlated with FGF-23. A significant association was seen between FGF-23 and BMD at the hip. Introduction: Circulating FGF-23 is elevated in CKD, although the primary stimulus remains unclear. Moreover, it is still unknown whether increase in FGF-23 has a biological effect on bone metabolism. The aim of the study was to investigate the association of FGF-23 with (1) the biochemical parameters linked with CKD-bone and mineral disorder (CKD-MBD) and (2) bone mineral density in CKD. Methods: We studied 145 patients (74 M, 71 F) aged (mean [SD]) 53 [14] years with CKD 1-4. Serum calcium, phosphate, parathyroid hormone, FGF-23, 25 (OH) vitamin D, 1, 25 (OH) vitamin D, bone turnover markers, CRP were determined. BMD was measured at the lumbar spine, femoral neck (FN), forearm, and total hip (TH). Multivariate analysis was undertaken to explore the association between (1) the biochemical variables and FGF-23 and (2) FGF-23 and BMD. Results: Elevations in FGF-23 occurred in CKD stage 3 compared to CKD stage 1/2, although no significant differences in serum phosphate were observed. Serum phosphate ( p < 0.001), CRP ( p < 0.001) and diabetes mellitus ( p < 0.05) were associated with FGF-23. BMD Z-score was significantly lower at the TH and FN in CKD 4 ( p < 0.05). A significant association was seen between BMI, FGF-23, bone specific alkaline phosphatase and BMD at the TH ( p < 0.05). Conclusions: The data suggest that FGF-23 may be associated with parameters implicated in the complications of CKD. Longitudinal studies are required for further clinical evaluation. [ABSTRACT FROM AUTHOR]

Summary: In the United Kingdom (UK), T- and Z-scores are usually calculated using reference ranges derived from United States (US) populations. In the UK arm of a recent randomised trial (International Breast Cancer Intervention Study II (IBIS-II)), substantially, fewer women than expected were recruited into the osteopenic $$ \left( { - {2}.{5} < {\hbox{T - score}} < - {1}.0} \right) $$ and osteoporotic (T-score <−2.5) arms of the study. The comparison with data from two independent studies showed that UK women aged >45 years with a typical body mass index of 28 kg m have spine and hip bone mineral density (BMD) 0.6 standard deviation higher than their US counterparts. Introduction: Dual energy X-ray absorptiometry (DXA) is widely used for the diagnosis of osteoporosis and to investigate the effect of pharmacological treatments on BMD. In both routine and research settings, it is important that DXA results are correctly interpreted. Methods: T- and Z-scores for the first 650 UK Caucasian women enrolled in the IBIS-II study were compared with data from two independent studies of unrelated, unselected UK Caucasian women: (1) 2,382 women aged 18 to 79 recruited to the Twins UK Adult Twin Registry; (2) 431 women aged 21 to 84 with no risk factors for osteoporosis recruited at Guy's Hospital. All DXA measurements were performed on Hologic densitometers. Subjects were divided into six age bands, and T- and Z-scores were calculated using the manufacturer's US reference range for the spine and the National Health and Nutrition Examination Survey III reference range for the femoral neck and total hip. Results: The overall mean Z-scores for the IBIS-II, Twin, and Guy's groups were: spine: +0.61, +0.29, +0.33; femoral neck: +0.42, +0.36, +0.45; total hip: +0.65, +0.38, +0.39 (all p < 0.001 compared with the expected value of 0). The mean body weight of subjects in the three studies was 74.4, 65.5, and 65.4 kg, respectively. Analysis revealed a highly significant relationship between Z-score and weight at each BMD site with a slope of 0.03 kg. Conclusions: In general, US spine and hip reference ranges are not suitable for the calculation of Z-scores in UK women. For some research study designs, the differences may significantly influence the pattern of subject recruitment. [ABSTRACT FROM AUTHOR]

Compares oral and implanted estrogens for the prevention of postmenopausal osteoporosis in Great Britain. Administration of oral treatment; Increase in bone density; Effectivity of subcutaneous estrogen than oral estrogen.

Osteoporosis is a common disease with a strong genetic component, characterized by reduced bone mass and increased fracture risk. Current evidence suggests that the inheritance of bone mass is under polygenic control but the genes responsible are poorly defined. Type I collagen is the major protein of bone encoded by the COLIA1 and COLIA2 genes. While these are strong candidates for the genetic regulation of bone mass, no abnormality of either gene has so far been defined in osteoporosis. In this study, we describe a novel G-->T polymorphism in a regulatory region of COLIA1 at a recognition site for the transcription factor Sp1(7) that is significantly related to bone mass and osteoporotic fracture. G/T heterozygotes at the polymorphic Sp1 site (Ss) had significantly lower bone mineral density (BMD) than G/G homozygotes (SS) in two populations of British women and BMD was lower still in T/T homozygotes (ss). The unfavourable Ss and ss genotypes were over-represented in patients with severe osteoporosis and vertebral fractures (54%), as compared with controls (27%), equivalent to a relative risk of 2.97 (95% confidence interval 1.63-9.56) for vertebral fracture in individuals who carry the 's' allele. While the mechanisms that underlie this association remain to be defined, the COLIA1 Sp1 polymorphism appears to be an important marker for low bone mass and vertebral fracture, raising the possibility that genotyping at this site may be of value in identifying women who are at risk of osteoporosis.