Effect of age and gender on serum periostin: Relationship to cortical measures, bone turnover and hormones

Periostin is an extracellular matrix protein, and in bone is expressed most highly in the periosteum. It increases bone formation through osteoblast differentiation, cell adhesion, Wnt signalling and collagen cross-linking. We hypothesised that serum periostin would be high at times of life when cortical modeling is active, in early adulthood and in older age, and that it would correlate with cortical bone measures, bone turnover and hormones that regulate cortical modeling. We conducted a cross-sectional observational study of 166 healthy men and women at three skeletal stages; the end of longitudinal growth (16–18 years), peak bone mass (30–32 years) and older age (over 70 years). We measured serum periostin with a new ELISA optimised for human serum and plasma which recognises all known splice variants (Biomedica). We measured the distal radius and distal tibia with HR-pQCT, and measured serum PINP, CTX, sclerostin, PTH, IGF-1, estradiol and testosterone. Periostin was higher at age 16–18 than age 30–32 (1253 vs 842 pmol/l, p < 0.001), but not different between age 30–32 and over age 70. Periostin was inversely correlated with tibia cortical thickness and density (R − 0.229, − 0.233, both p = 0.003). It was positively correlated with PINP (R 0.529, p < 0.001), CTX (R 0.427, p < 0.001) and IGF-1 (R 0.440, p < 0.001). When assessed within each age group these correlations were only significant at age 16–18, except for PINP which was also significant over age 70. We conclude that periostin may have a role in IGF-1 driven cortical modeling and consolidation in young adults, but it may not be an important mediator in older adults

Characterising variability and regional correlations of microstructure and mechanical competence of human tibial trabecular bone: An in-vivo HR-pQCT study.

OBJECTIVE: Quantifying spatial distribution of trabecular bone mechanical competence and microstructure is important for early diagnosis of skeletal disorders and potential risk of fracture. The objective of this study was to determine a spatial distribution of trabecular mechanical and morphological properties in human distal tibia and examine the contribution of regional variability of trabecular microarchitecture to mechanical competence. METHODS: A total of 340 representative volume elements at five anatomic regions of trabecular bone - anterior, posterior, lateral, medial and centre - from ten white European-origin postmenopausal women were studied. Region-specific trabecular parameters such as trabecular volume fraction, trabecular thickness, trabecular number, trabecular surface area, trabecular separation, plate-like structure fraction and finite element analysis of trabecular stiffness were determined based on in-vivo high resolution peripheral quantitative computed tomographic (HR-pQCT) images of distal tibiae from ten postmenopausal women. Mean values were compared using analysis of variance. The correlations between morphological parameters and stiffness were calculated. RESULTS: Significant regional variation in trabecular microarchitecture of the human distal tibia was observed (0.001 ≤ p ≤ 0.05), with up to 106% differences between lowest (central and anterior) and highest (medial and posterior) regions. Higher proportion of plate-like trabecular morphology (63% and 53%) was found in medial and posterior regions in the distal tibia. Stiffness estimated from finite element models also differed significantly (0.001 ≤ p ≤ 0.05), with stiffness being 4.5 times higher in the highest (medial) than lowest (central) regions. The bone volume fraction was the strongest correlate of stiffness in all regions. CONCLUSION: A novel finding of this study is the fact that significant regional variation of stiffness derived from two-phased FEA model with individual trabecula representation correlated highly to regional morphology obtained from in-vivo HR-pQCT images at the distal tibia. The correlations between regional morphological parameters and mechanical competence of trabecular bone were consistent at all regions studied, with regional BV/TV showing the highest correlation. The method developed for regional analysis of trabecular mechanical competence may offer a better insight into the relationship between mechanical behaviour and microstructure of bone. The findings provide evidence needed to further justify a larger-cohort feasibility study for early detection of bone degenerative diseases: examining regional variations in mechanical competence and trabecular specifications may allow better understanding of fracture risks in addition to others contributing factors

Clinical utility of bone turnover markers in monitoring the withdrawal of treatment with oral bisphosphonates in postmenopausal osteoporosis

Summary Bone markers may be useful to monitor response to treatment withdrawal in osteoporosis. We used two criteria for investigating the change in BTMs after withdrawal of bisphosphonate treatment. A larger increase in BTMs was associated with greater bone loss. Bone markers may be useful in monitoring of patients taking a pause from treatment. Introduction Measurement of bone turnover markers (BTMs) may be useful to monitor offset of treatment with bisphosphonates (BP) in osteoporosis. We assessed the effect of withdrawal of BP treatment by comparing the changes in BTMs and total hip (TH) bone density (BMD). Methods We studied postmenopausal osteoporotic women who had completed a randomised study of three oral BPs. After 2 years of treatment, participants with BMD T-score > − 2.5 and in whom it was considered clinically appropriate to discontinue treatment, were invited to participate in a further 2-year observational study. Biochemical response was assessed using BTMs (CTX and PINP) with offset being defined by two criteria: (1) an increase greater than the least significant change (LSC) and (2) an increase above the reference mean value. Results Fifty women completed the study. At 48 weeks after stopping BPs, CTX was greater than the LSC for 66% of women and PINP 72%; CTX was above the reference mean for 64% of women and PINP 42%. The decrease in THBMD was greater for women with the largest increase in BTM compared to those with continued suppression (mean difference for CTX was − 2.98%, 95%CI − 4.75 to − 1.22, P < 0.001, PINP − 2.25%, 95% CI − 4.46 to − 0.032, P = 0.046). Conclusion The measurement of BTM after withdrawal of BPs is potentially useful to evaluate patients that are taking a pause from treatment. An increase in BTMs more than the LSC and/or reference mean reflects loss of treatment effect and identifies patients that are likely to have a decrease in BMD. Such changes could provide an indication for reintroduction of treatment

Oxygen uptake kinetics in the frequency domain as a test for cardiorespiratory fitness

SIGLEAvailable from British Library Document Supply Centre-DSC:DXN023805 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

The impact of glucocorticoid therapy on trabecular bone score in older women

Summary: We propose that trabecular bone score could be a useful tool for the study of glucocorticoid-associated bone effects. Trabecular bone score alone and lumbar spine bone mineral density (BMD) used in combination with trabecular bone score, but not lumbar spine BMD alone was able to discriminate between glucocorticoid-treated and glucocorticoid-naïve women. Introduction: Glucocorticoids result in rapid bone loss and an increase in fracture risk that cannot be fully explained by changes in BMD. Trabecular bone score (TBS) correlates with three-dimensional bone micro-architectural parameters and can be derived from grey-level variations within dual energy X-ray absorptiometry (DXA) scans. We propose that TBS could be a useful tool for the study of glucocorticoid-associated bone effects. Methods: We assessed the ability of lumbar spine BMD (LS-BMD), TBS, and LS-BMD with TBS (LS-BMD + TBS) to discriminate between healthy women and (i) glucocorticoid-treated women, and (ii) glucocorticoid-naïve women with recent fractures. Older women (n = 484, ages 55–79 years) who had (i) taken prednisolone ≥5 mg/day for >3 months (n = 64), (ii) sustained a recent fracture of the distal forearm (n = 46), proximal humerus (n = 37), vertebra (n = 30) or proximal femur (n = 28), or (iii) were healthy population-based women (n = 279) were recruited. LS-BMD was measured by DXA and TBS values were derived. Results: Compared to healthy, population-based women, women with recent fractures had lower LS-BMD (−0.34 to −1.38) and TBS (−0.38 to −1.04) Z-scores. Glucocorticoid-treated women had lower TBS Z-scores than glucocorticoid-naïve women (−0.80 versus 0) but their LS-BMD Z-scores did not differ (−0.13 versus 0). TBS alone (area under the receiver operating characteristic curve (AUC) = 0.721) and LS-BMD + TBS (AUC = 0.721), but not LS-BMD alone (AUC = 0.572) was able to discriminate between glucocorticoid-treated and glucocorticoid-naïve women. Conclusions: TBS provides additional information regarding glucocorticoid-associated alterations in bone quality. We conclude that TBS may be a useful tool for the further study of glucocorticoid-induced osteoporosis

Relationships between oxygen uptake kinetics and maximal oxygen uptake

[Extract] Oxygen uptake (VO₂) kinetics describe the characteristics of the rate of change of V0₂ in response to a change in work rate. Subjects attaining higher maximal oxygen uptake (V0₂max) have faster VO₂ kinetics (Eβfeld et al., 1987). The purpose of this study was to use the pseudo random binary sequence (PRBS) exercise test to examine the strength of the relationship between V0₂max and VO₂ kinetics in a homogenous group of young, healthy women

Quantitative computed tomography discriminates between postmenopausal women with low spine bone mineral density with vertebral fractures and those with low spine bone mineral density only: the SHATTER study

Summary Lumbar spine volumetric bone mineral density (BMD) measured using quantitative computed tomography (QCT) can discriminate between postmenopausal women with low areal BMD with and without vertebral fractures. QCT provides a 3D measure of BMD, excludes the vertebral posterior elements and accounts for bone size. This knowledge could contribute to effective treatment targeting of patients with low BMD. Introduction We evaluated the ability of lumbar spine bone mineral apparent density (BMAD), trabecular bone score (TBS) and volumetric bone mineral density (vBMD) to discriminate between postmenopausal women with low areal bone mineral density (aBMD) by dual-energy X-ray absorptiometry (DXA) with and without vertebral fractures. The discriminatory ability of lumbar spine aBMD was compared with that of BMAD, TBS and vBMD. Methods We studied three groups of postmenopausal women, i.e. group 1, aBMD T-score  − 1 and no vertebral fracture, age-matched to group 1 (n = 37). Lumbar spine aBMD was measured by DXA. BMAD was calculated using the DXA scan results. TBS was derived following DXA scan image reanalysis. Lumbar spine vBMD was assessed by quantitative computed tomography and Mindways Pro software. Differences in variables between groups 1, 2 and 3 were examined using general linear univariate modelling approaches. Area under the receiver operating characteristic (ROC) curve was calculated for BMAD, TBS and vBMD to determine the ability of lumbar spine measurement variables to discriminate between group 1 and group 2. A comparison of ROCs was performed. Results Lumbar spine BMAD and TBS measurement variables were similar for groups 1 and 2. However, vBMD was significantly lower in group 1 and could discriminate between those women with low aBMD with (group 1) and without vertebral fractures (group 2). Conclusions We conclude that lumbar spine vBMD may discriminate well between postmenopausal women with low aBMD with and without vertebral fractures as it provides a 3D measure of bone mineral density, excludes the posterior elements of the vertebrae and takes into account bone size. A unique feature of the SHATTER study is that groups 1 and 2 were matched for aBMD, thus our study findings are independent of aBMD. Furthermore, we observed that neither BMAD nor TBS could distinguish between women with low aBMD with and without vertebral fractures. The knowledge gained from the SHATTER study will influence clinical and therapeutic decision-making, thereby optimising the care of patients with and without vertebral and other fragility fractures

The effect of bisphosphosphonates on bone turnover and bone balance in postmenopausal women with osteoporosis: The T-score bone marker approach in the TRIO study

Postmenopausal osteoporosis is characterised by increased bone turnover and an imbalance between bone resorption and formation. Bisphosphonate treatment reduces bone turnover but their effect on bone balance is yet to be fully investigated. Using the T-score approach our aims were to: i) investigate the effects of oral nitrogen-containing bisphosphonates on bone balance and turnover in postmenopausal women with osteoporosis and ii) determine the relationship of the change in bone balance and turnover with the change in BMD at the lumbar spine and total hip. Women were recruited, mean age 67 years, and randomised to receive: ibandronate (n = 55, 150 mg/month), alendronate (n = 54, 70 mg/week) or risedronate (n = 56, 35 mg/week). They also received calcium and vitamin D daily. A fasting serum sample was collected at baseline and weeks 1, 2, 4, 12, 13, 48 and 96. The control group were 226 healthy premenopausal women receiving no treatments. PINP and CTX were measured using the iSYSIDS analyser and BMD (in g/cm2) of the lumbar spine and total hip were measured by DXA (Hologic Inc). PINP and CTX values were log10-transformed and normalised. T-scores were calculated using the mean and standard deviation from the premenopausal group. Bone turnover and bone balance were calculated from the T-scores. Mean levels (95% CI) of balance and turnover are shown in the table. The change in turnover at weeks 4, 12 and 48 was inversely correlated with the change in lumbar spine and total hip BMD at weeks 48 and 96, (p <.01 to p <.001). The change in balance at week 4 positively correlated with the change in total hip BMD at weeks 48, (p <.01). Bisphosphonates resulted in an initial positive balance and a reduction in turnover. Some of these changes were associated with increases in BMD. Bone turnover is a better predictor of BMD than bone balance

High-impact exercise stimulated localised adaptation of microarchitecture across distal tibia in postmenopausal women

Summary We provided evidence that a 6-month regular hopping exercise intervention can increase trabecular number and possibly trabecular volume fraction of the distal tibia. Our novel localised analysis demonstrated region-specific changes, predominantly in the anterior region, in postmenopausal women. Introduction The localisation of bone remodelling and microarchitectural adaptation to exercise loading has not been demonstrated previously in vivo in humans. The aim of this study is to assess the feasibility of using 3D image registration and high-resolution peripheral quantitative computed tomography (HR-pQCT) to investigate the effect of high-impact exercise on human trabecular bone variables and remodelling rate across the distal tibia. Methods Ten postmenopausal women were recruited for 6-month unilateral hopping exercises, with HR-pQCT scans taken of both exercise leg (EL) and control leg (CL) for each participant before and after the intervention. A 3D image registration was used to ensure measurements were taken at the same region. Short-term reproducibility tests were conducted prior to the assessment using identical setup. The results were assessed comparing CL and EL, and interaction (time × leg) using a two-way repeated measures analysis of variance (RM-ANOVA). Results Across the whole tibia, we observed significant increases in trabecular number (Tb.N) (+ 4.4%) and trabecular bone formation rate (tBFR) (3.3%), and a non-significant increase in trabecular bone volume fraction (BV/TV) (+ 1%) in the EL. Regional resorption was higher in the CL than the EL, with this difference being statistically significant at the lateral tibia. In the EL, tBFR was significantly higher in the anterior region than the medial but a trabecular bone resorption rate (tBRR) showed no significant regional variation. Conversely in the CL, both tBFR and tBRR were significantly higher in the anterior and lateral than the medial region. Conclusion We demonstrated that it was possible to detect exercise-related bone adaptation with 3D registration of HR-pQCT scan data. Regular hopping exercise increased Tb.N and possibly BV/TV across the whole distal tibia. A novel finding of the study was that tBFR and tBRR responses to loading were localised: changes were achieved by formation rate exceeding resorption rate in the exercise leg, both globally and at the anterior region where turnover was greatest. Trial registration clinicaltrials.gov: NCT0322570