Establishing reference intervals for bone turnover markers in healthy postmenopausal women in a nonfasting state.

In order to interpret bone turnover markers (BTMs), we need to establish healthy reference intervals. It is difficult to establish reference intervals for older women because they commonly suffer from diseases or take medications that affect bone turnover. The aims of this study were: (1) to identify diseases and drugs that have a substantial effect on BTMs; (2) to establish reference intervals for premenopausal and postmenopausal women; and (3) to examine the effects of other factors on BTMs in healthy postmenopausal women. We studied women aged 30-39 years (n=258) and women aged 55-79 years (n=2419) from a five-European centre population-based study. We obtained a nonfasting serum and second morning void urine samples at a single baseline visit. BTMs were measured using automated immunoassay analysers. BTMs were higher in patients with vitamin D deficiency and chronic kidney disease. Three or more BTMs were higher in women who were osteoporotic and at least two BTMs were lower in women who were oestrogen replete, taking osteoporosis treatments or having diseases known to affect bone turnover. These were used as exclusion criteria for selecting the populations for the reference intervals. The reference intervals for BTMs were higher in postmenopausal than premenopausal women. Levels of BTMs were not dependent on geographical location and increased with age

Effects of strontium ranelate and alendronate on bone microstructure in women with osteoporosis: Results of a 2-year study

Summary: Strontium ranelate appears to influence more than alendronate distal tibia bone microstructure as assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT), and biomechanically relevant parameters as assessed by micro-finite element analysis (μFEA), over 2years, in postmenopausal osteoporotic women. Introduction: Bone microstructure changes are a target in osteoporosis treatment to increase bone strength and reduce fracture risk. Methods: Using HR-pQCT, we investigated the effects on distal tibia and radius microstructure of strontium ranelate (SrRan; 2g/day) or alendronate (70mg/week) for 2years in postmenopausal osteoporotic women. This exploratory randomized, double-blind trial evaluated HR-pQCT and FEA parameters, areal bone mineral density (BMD), and bone turnover markers. Results: In the intention-to-treat population (n = 83, age: 64 ± 8years; lumbar T-score: −2.8 ± 0.8 [DXA]), distal tibia Cortical Thickness (CTh) and Density (DCort), and cancellous BV/TV increased by 6.3%, 1.4%, and 2.5%, respectively (all P < 0.005), with SrRan, but not with alendronate (0.9%, 0.4%, and 0.8%, NS) (P < 0.05 for all above between-group differences). Difference for CTh evaluated with a distance transformation method was close to significance (P = 0.06). The estimated failure load increased with SrRan (+2.1%, P < 0.005), not with alendronate (−0.6%, NS) (between-group difference, P < 0.01). Cortical stress was lower with SrRan (P < 0.05); both treatments decreased trabecular stress. At distal radius, there was no between-group difference other than DCort (P < 0.05). Bone turnover markers decreased with alendronate; bALP increased (+21%) and serum-CTX-I decreased (−1%) after 2years of SrRan (between-group difference at each time point for both markers, P < 0.0001). Both treatments were well tolerated. Conclusions: Within the constraints of HR-pQCT method, and while a possible artefactual contribution of strontium cannot be quantified, SrRan appeared to influence distal tibia bone microstructure and FEA-determined biomechanical parameters more than alendronate. However, the magnitude of the differences is unclear and requires confirmation with another metho

J Musculoskelet Neuronal Interact

Long-term bed-rest is used to simulate the effect of spaceflight on the human body and test different kinds of countermeasures. The 2nd Berlin BedRest Study (BBR2-2) tested the efficacy of whole-body vibration in addition to high-load resisitance exercise in preventing bone loss during bed-rest. Here we present the protocol of the study and discuss its implementation. Twenty-four male subjects underwent 60-days of six-degree head down tilt bed-rest and were randomised to an inactive control group (CTR), a high-load resistive exercise group (RE) or a high-load resistive exercise with whole-body vibration group (RVE). Subsequent to events in the course of the study (e.g. subject withdrawal), 9 subjects participated in the CTR-group, 7 in the RVE-group and 8 (7 beyond bed-rest day-30) in the RE-group. Fluid intake, urine output and axiallary temperature increased during bed-rest (p or = .17). Body weight changes differed between groups (p < .0001) with decreases in the CTR-group, marginal decreases in the RE-group and the RVE-group displaying significant decreases in body-weight beyond bed-rest day-51 only. In light of events and experiences of the current study, recommendations on various aspects of bed-rest methodology are also discussed

Effects of intervertebral disk behavior on the load distribution and fracture risk of the vertebral body

Osteoporosis is characterized by low bone mass and an increased fracture risk. Measurements of bone mass alone, however, will not provide adequate information about the fracture risk, because the trabecular architecture or spatial distribution of the bone density has an important effect on the strength. We have developed a method to estimate the tissue strength of trabecular bone directly from 3D reconstructed axial CT-scans in combination with a finite element model. The method provides the stress distribution throughout the structure which can be used as a measure for the strength and fracture risk of the bone. A matter of concern with this method are the external loading conditions placed on the vertebral body, which might be strongly affected by the behavior of the intervertebral disk. In this study we have tested the effects of various intervertebral disk models on the load distribution through the vertebral body. A 3D model of a vertebral body was developed based on serial axial CT-scans which were converted to a 3D finite element model. The model was augmented with intervertebral disks at the upper and lower endplates. The disks contained a nucleus and an annulus region. The properties of the nucleus were varied to study the effects of a healthy disk with a functional nucleus pulposus and a degenerated disk with virtually no load bearing of the nucleus pulposus. The methods introduced in this study can be used to estimate load transfer through the vertebral body directly from CT-scans and, thereby, assessing the fracture risk of the bone and thus the status of osteoporosi

Bone strength loss during long-term bed rest is related to bone loading history

Bed rest studies are an accepted model for simulating bone loss due to microgravity during space flights. In a previous 60 days bed rest study, we investigated the loss of bone mass and the microstructural degeneration at the distal radius and tibia using a high-resolution (HR) pQCT device1. In combination with micro-finite element (micro-FE) analyses, it was possible to also quantify the loss of strength during bed rest2. In that study large variations in loss of bone strength were found between subjects. For some subjects no loss of strength was found whereas for others strength was reduced by 6.5%. Although these values are small and thus may not increase the risk of fracture, it may cause premature age-related osteoporosis and understanding the fundamental nature of the skeletal response to unloading is of great interest to develop countermeasures for overcoming the adverse effects of microgravity during spaceflights. In this study we investigate if the variation in loss of bone strength between subjects as observed in the earlier bed rest study could be related to their activity level prior to the bed rest. Since we expect that subjects that were more active would be more affected by the disuse, we hypothesized that the loss of bone strength is positively correlated to the physical activity of the subjects. As the activity level of the subjects prior to the bed rest study was not known, we used a recently developed method to estimate the bone loading history based on the bone architecture and correlated that with the loss in bone strength measured in the bed rest study to test our hypothesis