The effect of pulse steroid therapy on bone density and turnover: A systematic review and meta-analysis.

PurposeTo evaluate the influence of intravenous methylprednisolone (IVMP) pulse administration on bone mineral density (BMD) of the lumbar spine and the femoral neck in patients with moderate-to-severe Graves’ orbitopathy (GO).MethodsThirty-five patients with GO in euthyreosis were treated with 12 IVMP pulses (6 × 0.5 g, 6 × 0.25 g on a weekly schedule). Supplementation with 1.0 g of calcium and 800 IU of vitamin D was initiated in all patients before beginning therapy. BMD of the lumbar spine (L1–L4) and the femoral neck were assessed at baseline and after the last IVMP pulse using dual-energy X-ray absorptiometry. To determine differences in BMD between values at baseline and after treatment, we used the least significant change (LSC) methodology. LSC values were calculated to be 3 and 5% for the lumbar spine and the femoral neck, respectively. Change in BMD equal to or exceeding the LSC was assessed as either increase or decrease of BMD. We then compared pre-treatment and post-treatment mean BMD values at the lumbar spine and the femoral neck.ResultsWe did not observe a decrease of BMD at any site equal to or exceeding the LSC. We found an increase of BMD in at least one measurement site equal to or exceeding the LSC value in 43% of patients, mostly in the lumbar spine (31%). Mean femoral neck BMD did not change while mean lumbar BMD increased.ConclusionsIVMP given in weekly intravenous pulses does not lead to loss of BMD of the lumbar spine and the femoral neck.

There are limited studies regarding bone health among people living with HIV (PLHIV) in Asia. We compared bone mineral density (BMD), serum 25-hydroxyvitamin D (25(OH)D) status and bone turnover markers (serum procollagen type1 N-terminal propeptide (P1NP), osteocalcin (OC) and C-terminal cross-linking telopeptide of type1 collagen) among 302 antiretroviral therapy (ART) naive PLHIV compared to 269 HIV-uninfected controls from Thailand. People aged ≥30 years, with and without HIV infection (free of diabetes, hypertension, and active opportunistic infection) were enrolled. BMD at the lumbar spine, total hip, and femoral neck were measured using Hologic DXA at baseline and at 5 years. We analyzed BMD, serum 25(OH)D levels, and bone turnover markers at the patients’ baseline visit. PLHIV were 1.5 years younger and had lower BMI. PLHIV had higher mean serum 25(OH)D level and similar BMD to the controls. Interestingly, PLHIV had significantly lower bone formation (serum P1NP and OC), particularly those with low CD4 count. Only a few participants had low bone mass. ARV naïve middle-aged PLHIV did not have lower BMD or lower vitamin D levels compared to the controls. However, PLHIV had lower bone formation markers, particularly those with low CD4 count. This finding supports the benefit of early ART.

To determine the frequency of significant adverse effects associated with high-dose intravenous methylprednisolone therapy (HIVMP) given as methylprednisolone 1 g/d for three consecutive days. Retrospective study of consecutive patients. Department of Veterans Affairs Medical Center (VAMC), university teaching hospital, and private outpatient clinic. Eighty-four patients given HIVMP for systemic rheumatic disease. Subjective complaints were elicited via a standardized questionnaire that identified adverse effects through organ system review. Medical records were reviewed for adverse effects occurring within two weeks of HIVMP therapy. Two hundred seventy-five HIVMP treatments were examined by either patient questionnaire (76 patients) and/or chart review (78 patients). Sixty-five patients described symptoms after HIVMP treatment. Most symptoms were transient in duration, mild in severity, and required no medical treatment. Chart review found 42 possible complications occurring within two weeks of HIVMP therapy. In 18 instances medical intervention was required for problems that included hypertension, seizures, gastric erosions, sepsis, and other infections. It is impossible to attribute all of the complications to HIVMP alone because of underlying disease, use of other medications at the time of therapy, or both. HIVMP has an acceptably low risk of significant adverse effects.

PurposeVenous thromboembolic events (VTE), with their life-threatening manifestation as pulmonary embolism, are potential adverse effects of intravenous methylprednisolone (IVMP) pulse therapy, partially due to a hypercoagulable state. The aim of the study was to analyze the influence of IVMP on selected hemostatic parameters in patients with moderate-to-severe Graves’ orbitopathy (GO).Methods26 euthyroid patients with GO were treated with 12 pulses of IVMP (6 × 0.5, 6 × 0.25 g every week). Hemostatic variables [factor (F) II, FV, FVII, FVIII, fibrinogen, antithrombin, activated partial thromboplastin time (aPTT), prothrombin time, international normalized ratio of prothrombin time, platelets and D-dimer] were analysed before, 24 and 48 h after 1st, 6th and 12th pulse.ResultsA constant, transient trend in changes of some hemostatic variables was observed after all assessed pulses. We discovered an increase in median activity of FVIII 24 and 48 h after pulses, with a shortening of aPTT 24 h after each IVMP pulse (p < 0.00005). FVII decreased 24 h after each pulse (p < 0.0005 after 1st and 12th, p < 0.00005 after 6th). Fibrinogen level decreased 48 h after each pulse (P < 0.00005). We did not observe any statistically significant changes in hemostatic parameters in the long-term evaluation. Therapy was concluded in one patient after the 9th pulse due to pulmonary embolism.ConclusionsThe increase of FVIII activity is a consequence of treatment with IVMP and occurs after each pulse. In patients with additional risk factors of VTE, anticoagulation prophylaxis should be considered.

Consumption of nutrients and insulin resistance suppress markers of bone turnover in subjects with abdominal obesity.

Association between P1NP and bone strength in postmenopausal women treated with teriparatide

Association between changes in serum bone metabolism markers and bone microarchitecture changes during basic combat training – The ARMI study

Initiation of antiretroviral therapy, particularly of regimens that contain tenofovir disoproxil fumarate (TDF), results in increased bone turnover and a reduction in bone mineral density. In addition, TDF has been associated with increased parathyroid hormone (PTH) and efavirenz with reduced vitamin D [25(OH)D] concentrations [1]. The mechanism of bone loss in patients receiving TDF remains incompletely understood. A recent study by Hsieh et al.[2] examined changes in bone-regulatory hormones and bone biomarkers in a single-arm study of 134 antiretroviral therapy-naïve Chinese patients who initiated TDF, lamivudine and efavirenz. Consistent with previous studies, the authors observed statistically significant increases in PTH and bone turnover [collagen type 1 cross-linked C-telopeptide (CTx) and total procollagen type 1 N-terminal propeptide (P1NP)] at 24 and 48 weeks. Although no change in 25(OH)D was observed, vitamin D–binding protein concentrations increased from baseline, prompting the authors to propose a potential role for this plasma protein in TDF-associated bone loss. We recently completed a clinical trial with a similar focus on vitamin D, bone turnover and bone mineral density [3]. Sixty-four patients with well controlled HIV on TDF, emtricitabine and efavirenz were randomized to remain on their treatment or to switch antiretroviral therapy to darunavir/ritonavir for 48 weeks. The switching strategy was associated with significant increases in 25(OH)D concentration, reductions in bone turnover (CTx and P1NP) and a 2–3% increase in bone mineral density at the hip, femoral neck and lumbar spine. Notably, the reductions in CTx and P1NP and the improvement in bone mineral density occurred in the absence of changes in vitamin D–binding protein (Fig. 1), PTH, estimated glomerular filtration rate or renal tubular function [3].Fig. 1: Plasma vitamin D binding protein concentrations in the MIDAS trial [3].DRV/r, darunavir/ritonavir; EFV, efavirenz; FTC, emtricitabine; TDF, tenofovir disoproxil fumarate.Our results, as well as those of Hsieh et al.[2], are consistent with a direct effect of TDF on bone [4]. Although the increased bone turnover observed by Hsieh et al. may be the result of increased PTH concentrations with TDF exposure, the reduction in bone turnover markers in our patients who discontinued TDF was not accompanied by a reduction in PTH levels. The improved vitamin D status in our patients who switched therapy may have contributed to the decrease in bone turnover; however, the increase in bone mineral density in those switching off TDF was not explained by the increase in 25(OH)D, and the study by Hsieh et al.[2] demonstrates that TDF-induced increases in bone turnover may occur in the absence of changes in 25(OH)D status. Severe proximal tubulopathy may result in osteomalacia [5]. Both our data and those of Hsieh et al.[2] confirm that TDF-associated changes in bone turnover markers (and in our study, bone mineral density) may occur in the absence of changes in renal tubular function [6]. Moreover, our data do not support the hypothesis that TDF causes an increase in vitamin D–binding protein concentration, nor do they suggest that reductions in vitamin D–binding protein contribute to the improved bone mineral density that was observed following TDF discontinuation. Acknowledgements Conflicts of interest There are no conflicts of interest.

Background: Systemic therapies for breast cancer (BC) can lead to cancer treatment-induced bone loss (CTIBL), increase fracture risk, impair the quality of life, and potentially worsen prognosis. Although CTIBL prevention has been established in postmenopausal patients with BC, CTIBL in premenopausal women remains unclear owing to the limited number of reports. Chemotherapy often induces ovarian suppression and estrogen deficiency, thereby accelerating bone loss. Furthermore, the effects of tamoxifen on the bone are yet to be established in premenopausal patients with BC. In this study, we prospectively evaluated CTIBL in premenopausal patients with BC by monitoring bone mineral density (BMD), hormones, and bone turnover markers. Methods: We recruited 64 premenopausal females diagnosed with early-stage BC. We compared patients receiving tamoxifen monotherapy (T group, n=19; median age, 45 [range, 37-55] years) with those receiving chemotherapy followed by tamoxifen therapy (C group, n=31; median age, 45 years [range, 31-50] years). BMD at the lumbar spine and femoral neck was measured at baseline, immediately after chemotherapy (C group), and at 6, 12, and 18 months after tamoxifen initiation. Serum levels of estradiol (E2), follicle-stimulating hormone (FSH), bone turnover markers, procollagen type 1 N-terminal propeptide (P1NP), tartrate-resistant acid phosphatase 5b (TRACP-5b), and undercarboxylated osteocalcin (ucOC) were concurrently assessed to evaluate hormonal and metabolic effects on bone health. Results: 1. BMD Changes: T group: The changes(±SD) in BMD were minimal, with a 2.2±5.1% decrease (p=0.13) at the lumbar spine and a 1.6±4.4% increase(p=0.19) at the femoral neck at 24 months.C group: Lumbar spine BMD decreased by 2.4±3.9% post-chemotherapy (p=0.0057) and by 3.4±3.1% at 24 months (p=0.0060). Femoral neck BMD decreased by 1.3±4.6% post-chemotherapy (p=0.24) and 4.1±4.1% at 24 months (p=0.0047). 2. Hormonal Changes: T group: E2 increased by 328.1±385.6% at 6 months (p=0.003) but returned to baseline by 24 months. FSH levels showed no significant changes.C group: E2 decreased by 76.2±49.6% post-chemotherapy (p&amp;lt;0.001), with no significant differences observed at 24 months. FSH increased by 1061.1±890.7% post-chemotherapy (p&amp;lt;0.001), gradually decreased, and remained 53.6±89.8% above baseline at 24 months (p=0.038). 3. Bone Turnover Markers: T group: P1NP and TRACP-5b levels showed no significant changes over 24 months (all p &amp;gt; 0.05). ucOC decreased by 22.6±36.5% at 6 months (p=0.036), stabilizing thereafter.C group: P1NP increased by 98.9±90.0% post-chemotherapy (p&amp;lt;0.001) and gradually returned to baseline levels by 24 months (-5.4±45.0%, p=0.90). TRACP-5b increased by 89.9±106.6% post-chemotherapy (p&amp;lt;0.001) and gradually returned to baseline levels by 24 months (5.7±44.3%, p=0.38). ucOC decreased by 82.6±11.5% post-chemotherapy (p&amp;lt;0.001) and remained suppressed, with no significant recovery observed at 24 months (-89.1±9.2%, p&amp;lt;0.001). Conclusions: The C group showed significant and sustained reductions in BMD. The observed bone loss could be attributed to chemotherapy-induced ovarian suppression and estrogen deficiency. Increased bone turnover markers were consistent with a high bone resorption state and bone loss. Conversely, BMD was preserved in the T group, consistent with stable hormone levels and bone turnover markers. These findings indicate the need for proactive bone health management, including regular BMD monitoring and consideration of bone-protective treatments, especially in premenopausal patients with BC receiving chemotherapy, to improve long-term quality of life without fracture. Citation Format: A. Nishikawa, K. Narui, Y. Fujiwara, Y. Shibata, S. Adachi, K. Kawashima, M. Oshi, A. Yamada, H. Yoshikata, T. Tsuburai, I. Endo. Effects of cancer treatment on bone mineral density in premenopausal patients with early-stage breast cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-03-18.

Romosozumab increases bone mineral density in postmenopausal Japanese women with osteoporosis: A phase 2 study

Dear Editor, The study by Shuhaibar et al. [1] caught our attention because we have collected bone mineral density (BMD) data from multiple sclerosis (MS) patients recently. The authors report z scores significantly higher than zero in MS patients receiving immunomodulatory treatment (IMT) and conclude that IMT may have a favourable effect on bone in patients with MS. They did not compare their measurements in 37 MS patients receiving IMT with patients not receiving such treatment nor with healthy controls. We have measured BMD at, amongst other sites, the lumbar spine and proximal femur in 86 ambulant MS patients age 19–50 [40.1 ± 7.0 (mean ± SD) years]. A total of 39 patients (45%) were on IMT with interferon beta-1a (31), interferon beta-1b (4) or glatiramer acetate (3). Mean duration of treatment with the current IMT was 3.7 ± 2.4 years. Comparing patients on IMT with those not receiving IMT, there were no statistically significant differences between groups in age, duration of MS, EDSS, body mass index (BMI) or proportion treated with pulsed intravenous methylprednisolone. We have performed BMD measurements on a Lunar prodigy densitometer. Z scores are calculated using scanner software. The population the reference database is based on differs between manufacturers and may differ from the population studied. In northern Norway, we found mean z scores significantly lower than zero in both the IMT group (one-sample t test lumbar spine: P = 0.021, total hip: P = 0.011) and in the group not receiving IMT (total hip: P = 0.015, lumbar spine: ns). Measured z scores did not differ between IMT-treated and untreated patients (twosample t test lumbar spine: P = 0.653, total hip: P = 0.944). We do not wish to publish detailed data at this point. Our IMT-treated group is comparable with the patients studied by Shuhaibar et al. regarding most variables, except that our patients had longer duration of MS from first relapse (9.7 ± 7.0 vs. 5.8 ± 3.7 years) and slightly lower EDSS (median 2.5, mean 2.6 ± 1.2 vs. 3.1 ± 1.9). Fewer patients in our study had been treated with pulsed intravenous methylprednisolone (46 vs. 81%) and none had ever received long-term steroid treatment. Shuhaibar et al. do not provide information on BMI in their patients, although it is known that BMI has a strong positive association with BMD. Median BMI in our study was 25 for women and 27 for men. Minor differences in patient characteristics between the two studies are not a likely explanation for the conflicting results, whereas the densitometer software used might play a role. Shuhaibar et al. present the intriguing hypothesis that IMT treatment for MS may offer an unexpected benefit in terms of preventing osteoporosis, which they argue is biologically plausible. Our findings do not support this prediction. Based on our understanding of the literature and our own preliminary results, we consider it likely that MS is a cause of secondary osteoporosis and that there is no association between IMT and BMD. More research is definitely warranted in this area. M. T. Kampman (&) Department of Neurology, University Hospital of North Norway, P.O. Box 33, 9038 Tromso, Norway e-mail: margitta.kampman@unn.no

BackgroundTo investigate whether thoracolumbar kyphosis (TLK) of the spine is related to the reduction of bone mineral density (BMD) in postmenopausal osteoporosis women, and whether BMD of postmenopausal osteoporosis women can predict the occurrence of TLK.MethodsThis retrospective cohort study included 224 postmenopausal female patients hospitalized for osteoporosis from December 2017 to December 2020, and the control group included 270 postmenopausal female patients hospitalized for thoracolumbar degenerative diseases. The age, body mass index (BMI), visual analogue scale (VAS), and BMD of the lumbar spine [BMD(L)] and femoral neck [BMD(F)] of all patients during admission were recorded. We measured and recorded the Cobb angle of thoracolumbar and the height of the thoracolumbar intervertebral space in the spinal X-ray lateral radiograph. The Pearson and Spearman correlation coefficients were used to calculate the correlation between each parameter in the group. The Chi-square test was used for categorical variables, the independent-sample t-test was used for normally distributed continuous variables, and two-sample non-parametric tests were used for non-normally distributed variables. Binary logistic regression analysis and receiver operating characteristic (ROC) curves were applied to determine independent risk factors and cut-off values, respectively.ResultsThere were significant differences in the BMD(L), BMD(F), thoracolumbar junction Cobb angle, lumbar spine Cobb angle, T11/12-L1/2 height difference of the posterior and anterior edge of intervertebral space (HDPAIS), single vertebra Cobb angle (SVC), procollagen type 1 N-terminal propeptide (PINP) and 25-hydroxyvitamin D [25-(OH)D] between the study and control groups. Through binary logistic regression analysis, we found that BMD(L), PINP, bone alkaline phosphatase, and 25-(OH)D were independent risk factors for future TLK in postmenopausal women. According to the ROC curve, the prediction accuracy of BMD(L) was the highest. By calculating the critical value, we found that when the BMD(L) T-score <−1.65, postmenopausal women were more likely to develop TLK.ConclusionsIn postmenopausal osteoporosis patients, TLK will occur even if there is no compression fracture, and when the BMD(L) T-score <−1.65, postmenopausal women are more likely to develop TLK in the future.

Background/Objectives: Osteoporosis is a major public health concern, due to its high risk of fractures and disability and associated medical costs. Romosozumab, an anabolic agent, has been approved for the treatment of osteoporosis in postmenopausal women at high risk of fractures. However, limited data exist on its long-term effects in the Korean population, particularly regarding its impact on bone mineral density (BMD), bone turnover markers, and body composition. This study aimed to evaluate the 12-month effects of romosozumab treatment on BMD, bone turnover markers, and body composition in postmenopausal Korean women with high-fracture-risk osteoporosis (T-scores ≤ -3.0). Additionally, the impact of concomitant postmenopausal hormone therapy (MHT) on BMD changes was assessed. Methods: This multicenter, retrospective observational study included 50 postmenopausal women diagnosed with osteoporosis (T-scores ≤ -3.0) who received 12 monthly doses of romosozumab (210 mg) at two hospitals in Korea. Changes in BMD in the lumbar spine, femoral neck, and total hip were assessed using dual-energy X-ray absorptiometry (DXA). Bone turnover markers, including procollagen type 1 N-terminal propeptide (P1NP) and C-terminal telopeptide of type 1 collagen (CTX), were measured at baseline and at 3, 6, and 12 months. Changes in body composition, including the skeletal muscle index (SMI), body mass index (BMI), and visceral adipose tissue (VAT), were also analyzed. Results: After 12 months of romosozumab treatment, BMD significantly increased at the lumbar spine (14.65%), femoral neck (6.58%), and total hip (4.19%) (p < 0.05). P1NP levels increased significantly at 3 months (+37.9%), but returned to baseline at 6 months, while CTX levels continuously decreased (-27.8%) over 12 months. No significant changes were observed in SMI or BMI, but the VAT showed a slight decreasing trend (p < 0.05). Additionally, patients receiving concomitant MHT demonstrated a significantly greater increase in lumbar spine BMD compared to those receiving romosozumab alone (p < 0.05), while no significant differences were observed in femoral neck and total hip BMD. Conclusions: This study demonstrated that 12 months of romosozumab treatment significantly improved BMD and bone turnover markers in postmenopausal Korean women with severe osteoporosis. The combination of romosozumab and MHT further enhanced lumbar spine BMD gains. These findings support the use of romosozumab as an effective treatment for high-risk osteoporotic fractures in postmenopausal Korean women, and suggest potential benefits of a combined therapeutic approach.

ABSTRACTThe serum bone turnover markers (BTM) procollagen type 1 N‐terminal propeptide (P1NP) and C‐terminal cross‐linking telopeptide of type 1 collagen (CTX) are recommended for monitoring adherence and response of antiresorptive drugs (ARD). BTM are elevated about 1 year after fracture and therefore BTM target values are most convenient in ARD treatment follow‐up of fracture patients. In this prospective cohort study, we explored the cut‐off values of P1NP and CTX showing the best discriminating ability with respect to adherence and treatment effects, reflected in bone mineral density (BMD) changes. Furthermore, we explored the ability of BTM to predict subsequent fractures and BTM variation during daytime in patients using ARD or not. After a fragility fracture, 228 consenting patients (82.2% women) were evaluated for ARD indication and followed for a mean of 4.6 years (SD 0.5 years). BMD was measured at baseline and after 2 years. Serum BTM were measured after 1 or 2 years. The largest area under the curve (AUC) for discrimination of patients taking ARD or not was shown for P1NP <30 μg/L and CTX <0.25 μg/L. AUC for discrimination of patients with >2% gain in BMD (lumbar spine and total hip) was largest at cut‐off values for P1NP <30 μg/L and CTX <0.25 μg/L. Higher P1NP was associated with increased fracture risk in patients using ARD (hazard ratio [HR]logP1NP = 15.0; 95% confidence interval [CI] 2.7–83.3), p = 0.002. P1NP and CTX were stable during daytime, except in those patients not taking ARD, where CTX decreased by 21% per hour during daytime. In conclusion, P1NP <30 μg/L and CTX <0.25 μg/L yield the best discrimination between patients taking and not taking ARD and the best prediction of BMD gains after 2 years. Furthermore, higher P1NP is associated with increased fracture risk in patients on ARD. BTM can be measured at any time during the day in patients on ARD. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Aims To explore the relationships of procollagen type 1 N-terminal propeptide (P1NP) and β cross-linked C-telopeptide of type 1 collagen (β-CTX) with bone mineral density (BMD) in postmenopausal women. Methods All postmenopausal women were selected from a community-based case-control study. The anteroposterior L1-L4 and left proximal femur BMD were measured. P1NP and β-CTX were also collected and tested. The main correlation analysis was applied to explore the relationships of BMD, P1NP, and β-CTX. Results The total 1055 postmenopausal women were enrolled. The BMD at all sites kept a decrease continually with age (P < 0.01). In addition, the level of β-CTX increased significantly from 45 to 50 years old and remained at a high level in the later stage, while the level of P1NP changed little or even decreased with age. Logistic regression model showed that β-CTX has better ability to predict BMD than P1NP, as demonstrated by an area under the curve (AUC) of 0.63. Conclusion P1NP and β-CTX are important markers to monitor bone metabolism. This trial is registered with ChiCTR-SOC-17013090. The date of registration is Oct. 23, 2017.