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

The clinical utility of TRACP-5b to monitor anti-resorptive treatments of osteoporosis

Summary TRACP-5b can be used to monitor the response of treatments in osteoporosis. We investigated the effect of feeding on levels of TRACP-5b and how these markers perform in a clinical setting. After feeding, there was no effect on levels TRACP-5b. It has similar diagnostic accuracy to CTX and PINP. Introduction Bone turnover markers (BTMs) can be used to monitor response to osteoporosis treatment. However, some are affected by food intake and are not suitable to measure in a clinical setting. An assay is available which is capable of detecting the active isoform 5b of tartrate resistance acid phosphatase (TRACP-5b) and it may have minimal biological variation. Our aims were to investigate the effect of feeding on levels of TRACP-5b and compare this to CTX and PINP and then to compare the diagnostic accuracy of TRACP-5b to CTX and PINP in patients with osteoporosis given commonly used treatments. Methods Eighteen patients were recruited to investigate the effect of feeding on BTMs. Ninety-seven patients (74 females and 23 males) receiving 5 mg annual intra-venous zoledronate (mean age 70) and 97 patients receiving no treatment were recruited as group-matched controls. Sixteen patients receiving 60 mg subcutaneous denosumab every 6 months, (mean age 76) and 16 matched controls were recruited. Seventy-six patients were receiving oral bisphosphonates: 70 mg alendronate weekly, 35 mg risedronate and 150 mg monthly ibandronate (4%). Thirty of these patients had BMD measured at the total hip and lumbar spine. An estimate of compliance was not determined. Eighty patients receiving no treatment were recruited as group-matched controls. TRACP-5b (ELISA, Nittobo) and CTX and PINP were measured in serum in the non-fasting state between 0800 and 1700. Results After feeding, there was no effect on levels TRACP-5b and significant reductions in CTX and PINP, 29% and 10%, respectively (p < 0.001). In the zoledronate and denosumab groups, there were no differences in the areas under the curves (AUCs) between TRACP-5b, PINP and CTX. In the oral bisphosphonates group, the AUCs between TRACP-5b and PINP and TRACP-5b and CTX were significantly different, p < 0.01 and p = 0.001, respectively. TRACP-5b was negatively correlated with BMD. Conclusion TRACP-5b is not affected by food intake, unlike CTX and PINP. All three BTMs correlate with change in BMD at the lumbar spine and total hip. TRACP-5b has similar diagnostic accuracy to CTX and PINP with commonly used treatments for osteoporosis with the exception of oral bisphosphonate therapy

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

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

Prevention of bone loss with risedronate in glucocorticoid-treated rheumatoid arthritis patients

The aim of the study was to assess risedronate's effect on bone mineral density in postmenopausal women with rheumatoid arthritis receiving glucocorticoids. We carried out a two center, 2 year, double-masked, placebo-controlled trial with a third year of nontreatment follow-up. We studied 120 women requiring long-term glucocorticoid therapy at > 2.5 mg/day prednisolone randomized to treatment with daily placebo; daily 2.5 mg risedronate; or cyclical 15 mg risedronate (2 out of 12 weeks). At 97 weeks, bone mineral density was maintained at the lumbar spine (+1.4%) and trochanter (+0.4%) in the daily 2.5 mg risedronate group, while significant bone loss occurred in the placebo group (-1.6%, p = 0.03; and 4.0%, p &lt; 0.005, respectively). At the femoral neck, there was a nonsignificant bone loss in the daily 2.5 mg risedronate group (-1.0%) while in the placebo group bone mass decreased significantly (-3.6%, p &lt; 0.001). The difference between placebo and daily 2.5 mg risedronate groups was significant at the lumbar spine (p = 0.009) and trochanter (p = 0.02) but did not reach statistical significance at the femoral neck. Although not significantly different from placebo at the lumbar spine, the overall effect of the cyclical regimen was similar to that of the daily 2.5 mg risedronate regimen. Treatment withdrawal led to bone loss in the risedronate groups that was significant at the lumbar spine. A similar number of patients experienced adverse events (including upper gastrointestinal events) across treatment groups and risedronate was generally well tolerated. Thus risedronate preserves bone mass in postmenopausal women with rheumatoid arthritis receiving glucocorticoids while patients receiving a placebo have significant bone loss