Objective: Bone loss and periosteal expansion is found after menopause. The accelerated early postmenopausal bone loss is not permanent but if the same accounts for the periosteal expansion is unknown. Methods: Bone mineral density (BMD) and skeletal structure of the distal forearm were followed from menopause and on average 24 years (range 18-28) by single-photon absorptiometry at 12 occasions in a population-based sample of 81 Caucasian women with no medication or disease affecting bone metabolism. A Strength Index based on areal BMD and bone structure was calculated. Postmenopausal serum-estradiol levels and incident distal radius fractures were registered. Data are presented as means with 95% confidence interval (95% CI). Results: The annual BMD loss in three periods, 0-8, 8-16 and 16-28 years after menopause, was 2.0% (1.6, 2.4), 1.0% (0.6, 1.4) and 1.0% (0.7, 1.3), respectively. The annual periosteal expansion was 1.0% (0.8, 1.3), 0.0% (-0.3, 0.3) and 0.0% (-0.2, 0.2), respectively. Mean post-menopausal oestrogen levels correlated moderately with annual loss in aBMD (r=-0.51, p<0.001) but less with the annual changes in bone width (r=-0.22, p=0.06). Conclusion: Postmenopausal periosteal expansion in the distal forearm seems to occur only in the first postmenopausal decade.

Objectives: The objectives of this study were to examine the effects of voluntary exercise during pregnancy on maternal post-lactation bone parameters and offspring growth. Methods: Pregnant Wistar rats were housed in conventional cages (control), or were housed in raised cages requiring them to rise to an erect, bipedal stance to obtain food/water, throughout pregnancy. Dual energy X-ray absorptiometry and peripheral quantitative computed tomography scans were performed pre-mating and post-weaning. Maternal stress was assessed by fecal corticosterone measurement. Offspring weights were assessed at postnatal days 1 and 25 (weaning). Results: Changes in bone mineral over the pregnancy/lactation period were site-specific. Exercise did not affect loss of bone mineral from the lumbar spine, but did attenuate the loss of trabecular bone mineral from the tibial metaphysis and enhance the strength strain index and cross-sectional moment of inertia at the tibial diaphysis (P≤0.05) in dams in the exercised group. Fecal corticosterone did not differ between dam groups. There were no significant differences in offspring weight between the exercised and control group at either time point. Conclusions: Voluntary exercise in the pregnant rat can improve some post-lactation bone parameters and does not adversely affect early postnatal outcomes of the offspring.

Objectives: Neuropeptide Y (NPY) is a peptide involved in the regulation of appetite and energy homeostasis. Genetic data indicates that NPY decreases bone formation via central and peripheral activities. NPY is produced by various cell types including osteocytes and osteoblasts and there is evidence suggesting that peripheral NPY is important for regulation of bone formation. We sought to investigate the role of bone-derived NPY in bone metabolism. Methods: We generated a mouse where NPY was over-expressed specifically in mature osteoblasts and osteocytes (Col2.3NPY) and characterized the bone phenotype of these mice in vivo and in vitro. Results: Trabecular and cortical bone volume was reduced in 3-month-old animals, however bone formation rate and osteoclast activity were not significantly changed. Calvarial osteoblast cultures from Col2.3NPY mice also showed reduced mineralization and expression of osteogenic marker genes. Conclusions: Our data suggest that osteoblast/osteocyte-derived NPY is capable of altering osteogenesis in vivo and in vitro and may represent an important source of NPY for regulation of bone formation. However, it is possible that other peripheral sources of NPY such as the sympathetic nervous system and vasculature also contribute to peripheral regulation of bone turnover.

Mechanography is an innovative method to evaluate lower-limb dynamic muscle function. This technique is generally performed on force platforms that measure only the vertical component of ground reaction force (GRF). The underlying assumption is that medio-lateral and antero-posterior forces do not contribute significantly to the GRF in jumping and rising tests. The goal of this study was to establish the validity of this assumption. Fifteen healthy adults (mean age [SD]: 30 [11] years; mean height [SD]: 1.68 [0.12] m; mean body mass: 70 [18] kg) performed three repetitions of five different tests in the following order: multiple two-legged hopping, multiple one-legged hopping, single two-legged jump, heel-rise test and chair-rise test. An excellent agreement was found between peak GRF and peak vertical GRF. In each of the five tests, peak vertical GRF represented more than 99% of peak GRF. Moreover, the limits of agreement ranged between 0.05% (multiple two-legged hopping test) and 0.4% (heel-rise test) of the averaged peak force measurements. Therefore measuring only the vertical component of ground reaction force in healthy participants is appropriate for the five tests used in the present study.

Objectives: To determine longitudinal changes in trabecular volumetric BMD (vBMD) at tibia and radius in young depressive patients under antidepressants using pQCT. Methods: pQCT data on 26 patients (22 females, 4 males) on serotonin re-uptake inhibitors (SSRI), and 14 patients (12 females, 2 males) on non-SSRI (10 SNRI, 4 TCA) were obtained at 4% and 66% of radius and tibia at baseline and at 12-month. Depression was assessed by Beck Depression Inventory (BDI) at baseline and follow-up. Wilcoxon tests were performed to find longitudinal changes in bone parameters within each group, Mann-Whitney tests to detect differences between groups. Results: The two groups were comparable with regard to age, height and BDI. None of the measured bone parameters changed in the SSRI group. In the non-SSRI group trabecular vBMD increased slightly but significantly from baseline to follow-up at radius and tibia (p<0.03). Between group differences were significant for trabecular BMD at the radius. BDI decreased significantly in both groups by the same amount. Conclusions: Bone properties were found to be stable over 12 months under therapy with SSRIs. Whether SNRI and TCA indeed increase trabecular vBMD need to be shown in larger cohort.

Neurogenic heterotopic ossification (HO) is the ectopic formation of lamellar bone in non-osseous tissues following traumatic brain or spinal cord injury. The associated complications affect greatly their quality of life. This fact has shifted the focus of scientific effort towards the investigation and understanding of related risk factors and the pathophysiological mechanisms. Recent advancements include the investigation for genetic predisposition and association various biomarkers. In the present article we will analyze the current concepts on this topic, based on clinical and physiological evidence and we will discuss the potential areas for future research on this field.

Introduction: Preclinical studies with osteoprogenitor cells derived from human embryonic stem cells (hESC) do not lead to substantial bone regeneration in vivo. The degree of survival following implantation might play a role in their long term efficiency. We investigated the initial engraftment of hESCs-derived cells during two weeks post-implantation and compared it to such response for adult bone marrow stromal cells (hBMSC)-derived osteoprogenitor cells. Methods: hBMSC and H9-hES cells pre-treated with osteogenic factors were implanted into a calvarial defect in both adult WT and nude rats. At days 7 and 14 post-implantation, samples were analysed for persistence of implanted cells, initiation of regeneration of host bone, angiogenesis and apoptosis. Results: At day 7, hESC and hBMSC were detected within defects in both rat strains. By day 14 human cells were only detected in immune-deficient rats whilst still maintaining an osteoblastic phenotype and engendered a significant increase in bone formation. In WT animals, the participation of implanted cells was very limited due to their poor survival. Conclusion: This study demonstrates the ability of hESC and hBMSC derived osteoprogenitor cells to survive transplantation, to engraft and to develop an osteogenic phenotype during the early stage following implantation, validating the appropriate preclinical model.

Background: At feet with painless diabetic neuropathy (PDN) and a healed fracture (quiescent Charcot-foot), cutaneous pressure pain perception threshold (CPPPT) is elevated beyond the range of measurement, whereas deep pressure pain perception threshold (DPPPT) may be normal. It is unknown, how these thresholds behave under the conditions of a foot injury. We therefore measured CPPPT and DPPPT in the vicinity of a unilateral active foot injury. Patients and methods: 18 diabetic patients with PDN and plantar injury, partly involving the skeleton (Wagner grade I-II ulcer), 10 non-neuropathic subjects with acute painful skeletal injury (sprain, fracture) and 20 healthy control subjects without foot injury were studied. CPPPT was measured using calibrated monofilaments, and DPPPT was measured by Algometer II^® over muscle and joint. Results: Compared to control subjects, non-neuropathic acutely injured (and contralateral) feet displayed lowered CPPPT and DPPPT. Conversely, ulcerated and contralateral feet with PDN displayed unmeasurably elevated thresholds in 100% (CPPPT), 72% (DPPPT over joint), and 28% (DPPPT over muscle) of patients, respectively. Conclusion: In the vicinity of an active foot injury, physiologic hyperalgesia was demonstrated in the non-neuropathic subjects, but not in the patients with PDN in whom neglect of foot trauma is, therefore, common.