Trabecular bone microarchitecture predicts fragility fractures in postmenopausal women on denosumab treatment.

BACKGROUND: High-resolution peripheral quantitative computed tomography (HR-pQCT) represents a three-dimensional tool for the screening of osteoporosis patients i.e., regarding fracture risk. The purpose of this study was to determine the baseline and follow-up bone microarchitecture in relation to incident fracture risk in postmenopausal women on denosumab treatment. METHODS: We have retrospectively evaluated data from 182 postmenopausal women treated with denosumab that underwent an initial HR-pQCT scan before the initiation of the treatment; and at least one second HR-pQCT after 12 months. Women were assigned to two groups based on documented fragility fractures for the following 2.9 ±â€¯1.1 years: fracture (n = 22) and no fracture (n = 160). Baseline parameters from DXA, HR-pQCT and bone turnover were compared between the two groups. Furthermore, ROC and multiple regression analyses of the baseline and follow-up data were performed to evaluate the predictive value regarding incident fractures. RESULTS: At baseline, trabecular parameters were significantly reduced in the fracture group and showed the best predictive value for new fractures, while DXA results could not predict fractures. A multiple regression model identified BV/TV and age as the best baseline parameters for incident fracture risk. At 12 months, cortical and trabecular parameters increased in the non-fracture group, while no significant increase was noted in the fracture group. However, no significant differences regarding the changes of these parameters could be detected between the non-fracture and fracture cohort. CONCLUSIONS: Trabecular bone microstructure at baseline is crucial for incident fracture risk in postmenopausal women on denosumab treatment, especially in comparison to DXA values. In this context, the microstructural follow-up results seemed to be of lesser importance regarding fracture risk. The results of this exploratory study should be validated in independent populations.

Effect of vitamin D3 treatment on bone density in neurofibromatosis 1 patients: a retrospective clinical study.

OBJECTIVES: We have previously demonstrated reduced bone density and an increased incidence of 25-hydroxy vitamin D3 (25-OH D3) deficiency in adults with neurofibromatosis 1 (NF1) compared to healthy controls. Vitamin D3 is a cheap, safe, and effective supplement in the general population, but its value in NF1 patients has not been demonstrated. This study investigates the therapeutic potential of oral vitamin D3 on bone mineral density (BMD) in NF1 patients with vitamin D3 deficiency. METHODS: We measured serum 25-OH D3, parathyroid hormone, calcium, and bone alkaline phosphatase concentrations, urinary deoxypyridinoline concentrations, and BMD in 35 adults with NF1. Nineteen patients received vitamin D3 supplementation for 2 years, six patients received supplementation for 1 year and 10 patients received no supplementation. Supplementation was administered in a dose that maintained the serum 25-OH D3 level above 30 µg/l. BMD was measured again at 1 and 2 years, and biochemical assessments of bone metabolism were measured at least every half year during therapy. RESULTS: Treated subjects had significantly reduced loss of BMD, as measured by T score at the hip (p=0.011) and lumbar spine (p=0.022). The effect on hip BMD was apparent at 1 year in comparison to baseline (p=0.02) and was greater at 2 years in comparison to measurements at 1 year (p=0.02). CONCLUSIONS: Vitamin D3 supplementation improves BMD in adult NF1 patients. Further studies are needed to elucidate the mechanisms responsible for reduced BMD in NF1 patients.

Strontium ranelate and alendronate have differing effects on distal tibia bone microstructure in women with osteoporosis.

The structural basis of the antifracture efficacy of strontium ranelate and alendronate is incompletely understood. We compared the effects of strontium ranelate and alendronate on distal tibia microstructure over 2 years using HR-pQCT. In this pre-planned, interim, intention-to-treat analysis at 12 months, 88 osteoporotic postmenopausal women (mean age 63.7 +/- 7.4) were randomized to strontium ranelate 2 g/day or alendronate 70 mg/week in a double-placebo design. Primary endpoints were changes in microstructure. Secondary endpoints included lumbar and hip areal bone mineral density (aBMD), and bone turnover markers. This trial is registered with http://www.controlled-trials.com, number ISRCTN82719233. Baseline characteristics of the two groups were similar. Treatment with strontium ranelate was associated with increases in mean cortical thickness (CTh, 5.3%), cortical area (4.9%) and trabecular density (2.1%) (all P < 0.001, except cortical area P = 0.013). No significant changes were observed with alendronate. Between-group differences in favor of strontium ranelate were observed for CTh, cortical area, BV/TV and trabecular density (P = 0.045, 0.041, 0.048 and 0.035, respectively). aBMD increased to a similar extent with strontium ranelate and alendronate at the spine (5.7% versus 5.1%, respectively) and total hip (3.3% versus 2.2%, respectively). No significant changes were observed in remodeling markers with strontium ranelate, while suppression was observed with alendronate. Within the methodological constraints of HR-pQCT through its possible sensitivity to X-ray attenuation of different minerals, strontium ranelate had greater effects than alendronate on distal tibia cortical thickness and trabecular volumetric density.

High resolution computed tomography of the vertebrae yields accurate information on trabecular distances if processed by 3D fuzzy segmentation approaches.

INTRODUCTION: The structure of trabecular bone represents an aspect of bone properties that affects vertebral bone strength independently of bone mineral density [M. Kleerekoper, A. Villanueva, J. Stanciu, D. Rao, and A. Parfitt. The role of three-dimensional trabecular microstructure in the pathogenesis of vertebral compression fractures. Calcif. Tissue Int., 37:594-597, Dec 1985; E. Seeman and P. Delmas. Bone quality-the material and structural basis of bone strength and fragility. N. Engl. J. Med., 354:2250-2261, May 2006.]. Using the mathematical concept of fuzzy distance transformation (FDT), we evaluated the accuracy of measurements of trabecular distance (Tb.Di(f)) which can be determined for vertebrae in vivo using high resolution computed tomography (HRCT). METHODS: In a first step extrema voxels with a very high likelihood of representing bone or marrow are identified. A probability level of being a bone voxel is assigned to all other voxel. This probability is based on the FDT of the voxel's gray-level, preprint submitted to Elsevier June 10, 2008; revised July 15, 2008 i.e. the shortest gray-value weighted distance to the marrow background. Next, the resulting bone structure is skeletonized. The space between the ridges of the skeleton is filled with the largest possible spheres. The average over the radii of the spheres defines Tb.Di(f), a measure of trabecular distance. 14 whole vertebrae embedded in polymethyl methylacrylate were scanned by HRCT (voxel size 156 x 156 x 400 mum(3)) inside an anthropomorphic abdomen phantom. Scans obtained on Scanco Xtreme CT (XCT, voxel size 82(3) microm(3)) without the phantom were used as reference. RESULTS: Tb.Di(f) calculated on XCT data were almost identical to trabecular distance values (1/Tb.N*) determined with the manufacturer's standard software (r(2)=0.98). Tb.Di(f) values obtained with HRCT correlated strongly with Tb.Di(f) values obtained by XCT (r(2)=0.89). Over the range from 400 to 1400 microm trabecular distance could be estimated with a residual error of 78 microm. CONCLUSIONS: The FDT based variable Tb.Di(f) provides 3D estimates of trabecular distances with residual errors of less than 100 microm using a HRCT protocol which also can be employed in vivo for assessing vertebral microarchitecture.