Osteoporos Int
· 2026 Jun · PMID 42234035
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Osteoporosis is a systemic skeletal disorder traditionally attributed to imbalances in bone metabolism. Increasing evidence suggests that the intestinal environment and chronic inflammation play important roles in itspat...Osteoporosis is a systemic skeletal disorder traditionally attributed to imbalances in bone metabolism. Increasing evidence suggests that the intestinal environment and chronic inflammation play important roles in itspathogenesis. The gut-bone-inflammation axis provides a novel perspective for understanding the interactions among intestinal barrier function, immune regulation, and bone homeostasis. This review aims to summarize current evidence regarding the role of intestinal barrier disruption in osteoporosis and to discuss its contribution within the framework of the gut-bone-inflammation axis. Relevant experimental and clinical studies from the existing literature were reviewed and synthesized, with a focus on intestinal barrier integrity, gut microbiota dysbiosis, inflammatory mediators, immune activation, and bone metabolism. Disruption of the intestinal barrier increases intestinal permeability, facilitating the translocation of microbial products and pro-inflammatory mediators into the systemic circulation. This process promotes chronic low-grade inflammation, enhances osteoclast differentiation and activity, suppresses osteoblast function, and disrupts the balance of bone remodeling. Gut microbiota imbalance, immune activation, and sustained inflammatory signaling collectively contribute to bone loss and structural deterioration in osteoporosis. Intestinal barrier dysfunction plays a pivotal role in osteoporosis through modulation of systemic inflammation and bone metabolism. Strategies aimed at preserving intestinal barrier integrity and regulating the gut microbiota may offer promising preventive and therapeutic approaches for the management of osteoporosis.
Fu SC, Lu YC, Sie NH
… +5 more, Hung CC, Li CY, Yang RS, Fu SH, Wang CY
Osteoporos Int
· 2026 Jun · PMID 42228020
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UNLABELLED: This study evaluated whether prior anti-osteoporosis medication (AOM) use influences fracture risk in patients at very high fracture risk who subsequently initiated teriparatide. Using a nationwide cohort of...UNLABELLED: This study evaluated whether prior anti-osteoporosis medication (AOM) use influences fracture risk in patients at very high fracture risk who subsequently initiated teriparatide. Using a nationwide cohort of 14,770 patients, participants were categorized based on prior AOM exposure. Bisphosphonate was associated with decreased both fracture and spinal fracture-related hospitalization, while the decreased risk was not shown in denosumab users. Long-term denosumab use (≥ 3 years) was associated with a significantly increased risk of spine fracture-related hospitalization after transitioning to teriparatide. PURPOSE: To evaluate whether prior AOM use, including type and duration, affects fracture-related hospitalization in patients at very high fracture risk initiating teriparatide. METHODS: This nationwide cohort study used Taiwan's National Health Insurance Research Database (2013-2019) to examine 14,770 patients. Patients were categorized by prior AOM use (yes vs no), AOM type (bisphosphonates vs denosumab vs raloxifene; denosumab vs non-denosumab), and denosumab duration (≥ 3 vs < 3 years). The primary outcome was hospitalization for major osteoporotic fractures within 3 years. RESULTS: 9,127 participants received AOM treatment within 2 years prior to teriparatide initiation, whereas 5,643 did not. There was no statistically significant difference in fracture-related hospitalizations between the AOM and non-AOM groups (HR = 0.92; 95% CI 0.83-1.02; p = 0.102). However, the HR for spinal fracture-related hospitalization was lower in the AOM treatment group (HR = 0.85; CI 0.73 to 0.98; p = 0.026).] Bisphosphonate was associated with decreased both fracture and spinal fracture-related hospitalization, (HR = 0.85, 95% CI = 0.75-0.96 for fracture; HR = 0.83, 95% CI = 0.76-0.91 for spinal fracture), while the decreased risk was not shown in denosumab users. Noteworthy, patients who had used denosumab for ≥ 3 years before switching to teriparatide had a significantly higher risk of spine fracture--related hospitalizations (adjusted HR 1.86, p = 0.011), particularly within the first 6 months of transitioning (adjusted HR 1.98, p = 0.031). CONCLUSION: Prior AOM therapy was not associated with an increased fracture-related hospitalization risk after starting teriparatide in patients at very high fracture risk. However, among those who used AOM before teriparatide initiation, long-term denosumab use (≥ 3 years) was associated with an increased risk of spine fracture-related hospitalization. Further research is warranted to optimize sequential therapy strategies among patients under long-term denosumab use.
Hodwitz K, El-Hussein M, Cameron JI
… +8 more, Meadows LM, Watt J, Ashe M, Phan J, Aghajafari F, Funnell L, Verduyn A, Sale JEM
Osteoporos Int
· 2026 May · PMID 42165872
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UNLABELLED: The emotional experience of informal caregiving is considerable and complex, consisting of tensions internally and with the care recipient, and exacerbated by pressures to adopt the caregiver role without com...UNLABELLED: The emotional experience of informal caregiving is considerable and complex, consisting of tensions internally and with the care recipient, and exacerbated by pressures to adopt the caregiver role without complaint or assistance. Our findings demonstrate the need to develop policies to relieve distress for caregivers of fragility fracture patients. PURPOSE: Informal caregiving can have considerable physical and psychosocial consequences, with the emotional strain of caregiving considered most distressing. Few studies have examined the emotional experience of caregiving for individuals with a fragility fracture or the contextual factors that may influence this experience. We aimed to explore the experience of caring for someone after a fragility fracture to understand the nuances of the emotional experience and identify ways to better support informal caregivers in the future. METHODS: We used a phenomenological approach to examine caregivers' experiences. We recruited primary caregivers of patients discharged from a rehabilitation hospital following a fragility fracture. We conducted individual interviews with caregivers and analyzed the data phenomenologically to describe the structure of caregivers' emotional experiences and illuminate potential influencing factors. RESULTS: We interviewed 32 caregivers (19 females, 13 males; 37-95 years old). We found that the emotional experience of caregiving was complex, consisting of tensions internally and with care recipients, and exacerbated by multiple pressures to adopt the caregiver role. As a result of these pressures, caregivers often felt reluctant to voice displeasure or ask for help, exacerbating their burden and reinforcing a sense that they must suffer in silence. CONCLUSION: Our study demonstrates the multifaceted nature of caregivers' emotional burden and highlights the pressures felt by caregivers of fragility fracture patients to take on caregiving roles without complaint or assistance. Our findings highlight the need to acknowledge the emotional complexity of caregiving, empower caregivers to ask for help, and develop meaningful supports and policies to alleviate caregiver burden.
Osteoporos Int
· 2026 May · PMID 42162397
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UNLABELLED: People with type 2 diabetes mellitus (T2DM) accumulate factors that weaken bone. In over two million adults, fracture risk rose stepwise as diabetes progressed, with the steepest increase for hip fractures. A...UNLABELLED: People with type 2 diabetes mellitus (T2DM) accumulate factors that weaken bone. In over two million adults, fracture risk rose stepwise as diabetes progressed, with the steepest increase for hip fractures. A simple progression score using routine clinical data may help flag patients who need earlier bone-protective care. PURPOSE: Patients with type 2 diabetes mellitus (T2DM) are often exposed to multiple factors contributing to bone fragility-such as poor glycemic control, long duration of exposure to hyperglycemia, and comorbidities. Because these factors often accumulate over time, we examined whether fracture risk increases with diabetes progression. METHODS: We analyzed data from 2,069,920 patients with T2DM from the Korean National Health Information Database who underwent health examinations in 2015-2016. Patients with a prior history of fractures or who died within one year were excluded. Diabetes progression was scored from 0 to 6 based on the number of oral glucose-lowering drugs, disease duration, insulin use, and presence of chronic kidney disease, cardiovascular disease (CVD), or diabetic retinopathy. Incident fractures were tracked until 2023 using ICD-10 codes. RESULTS: Over a median follow-up of 6.4 years, 169,595 fractures occurred, including 69,723 vertebral and 23,581 hip fractures. Each component of diabetes progression was independently associated with fracture risk (hazard ratios [HRs] ranging from 1.14 to 1.40). Insulin use (HR, 1.40; 95% confidence interval [CI]: 1.38-1.42) and CVD (HR, 1.26; 95% CI: 1.24-1.28) conferred notably higher risks. Fracture risk increased progressively with higher progression scores (HRs for score 4: 1.60; 95% CI: 1.56-1.64; HRs for score 5: 1.87; 95% CI: 1.78-1.96). The magnitude of increase was more pronounced for hip fractures. CONCLUSION: The risk of fractures increased incrementally in parallel with diabetes progression, most notably for hip fractures. Diabetes progression metrics may help identify patients at elevated fracture risk.
Xu N, Liu P, Liu C
… +4 more, Zhu Z, Kang Y, Wang G, Chen F
Osteoporos Int
· 2026 May · PMID 42159645
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UNLABELLED: The primary objective of this study was to determine the differences in efficacy between denosumab and zoledronate in preventing secondary vertebral compression fractures (VCFs). Our findings demonstrate that...UNLABELLED: The primary objective of this study was to determine the differences in efficacy between denosumab and zoledronate in preventing secondary vertebral compression fractures (VCFs). Our findings demonstrate that twice-yearly administration of denosumab compared with conventional zoledronate significantly reduces the early risk of secondary VCFs among postmenopausal women following vertebroplasty. However, this advantage was confined to the first year and was not sustained at 24 months. Clinicians should consider denosumab as a preferential option over bisphosphonates when managing osteoporotic women at high risk of early secondary VCFs. BACKGROUND: Denosumab and zoledronate, both recognized as first-line antiresorptive agents, are among the most widely administered drugs for osteoporotic patients experiencing vertebral compression fractures (VCFs). To date, no head-to-head study has been individually powered to compare their efficacy in secondary VCF prevention. PURPOSE: To evaluate the comparative preventive efficacy of denosumab versus zoledronate against secondary VCFs in postmenopausal women with primary osteoporosis and pre-existing VCFs. METHODS: Postmenopausal women who underwent vertebroplasty for osteoporotic VCFs at our medical center were prospectively enrolled. Eligible participants were randomly assigned to receive either the denosumab regimen (Den-arm) or the zoledronate regimen (Zol-arm) following spinal intervention for a duration of 2 years. The primary endpoint was the occurrence of new morphometric VCFs identified on lateral radiographs. Secondary endpoints included new clinical VCFs, bone mineral density (BMD), and serum bone turnover markers. RESULTS: As of December 2025, complete study follow-up was confirmed for 313 subjects (155 randomized to the Den-arm and 158 to the Zol-arm). New morphometric VCFs occurred significantly less frequently in the Den-arm compared with the Zol-arm at 12 months (2.0% vs. 7.6%, P = 0.031), but the overall incidence was comparable at 24 months (5.8% vs. 8.2%, P > 0.05). The 24-month Kaplan-Meier analysis estimated a lower cumulative incidence of new clinical VCFs in the Den-arm versus the Zol-arm (2.0% vs. 6.9%, log-rank P = 0.030). Significant differences were observed in the percent change in lumbar BMD from baseline, favoring the Den-arm over the Zol-arm at 6 and 12 months after treatment initiation (P < 0.001 and P < 0.05, respectively). The Den-arm also showed greater decreases in the bone resorption marker s-CTX from baseline compared with the Zol-arm at 3 and 6 months after treatment (P < 0.05). CONCLUSION: Among postmenopausal women with prevalent osteoporotic VCFs, the administration of denosumab versus zoledronate demonstrated superior efficacy in preventing early secondary VCFs within the first year. However, this short-term advantage was not maintained at 24 months, as both agents showed comparable overall morphometric VCF incidence by the end of the study period. Further research with extended follow-up is warranted to clarify the long-term comparative efficacy of denosumab versus other anti-osteoporosis agents.
Goel H, Spector E, Yardley G
… +4 more, Mosiman S, Krueger D, Binkley N, Sibonga J
Osteoporos Int
· 2026 May · PMID 42154221
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UNLABELLED: Dual-energy X-ray absorptiometry (DXA) alone is not ideal for fracture risk assessment given its two-dimensional nature. We evaluated the 3D-Shaper software for its potential to detect an unappreciated hip tr...UNLABELLED: Dual-energy X-ray absorptiometry (DXA) alone is not ideal for fracture risk assessment given its two-dimensional nature. We evaluated the 3D-Shaper software for its potential to detect an unappreciated hip trabecular bone loss in astronauts. DXA-based 3D-Shaper software showed promising results as a screening tool while minimizing radiation exposure. INTRODUCTION: Prolonged spaceflight results in bone loss, as assessed by DXA performed before and after long-duration missions. Hip trabecular loss, detected by QCT but not DXA, persists in some astronauts for up to 2 years after 6-month missions. Since QCT increases radiation exposure, we evaluated a DXA software (3D-Shaper) as a screening method to identify astronauts in whom inadequate recovery of hip trabecular bone would be likely confirmed with QCT. METHODS: Hip data from 23 ISS astronauts (19 M/4F) with pre- and postflight QCT and DXA were analyzed. These scans were obtained pre-flight (within 4 months of launch), immediately post-flight (within 22 days of return), and 1-year post-flight (within 11-14 months). Left total hip data by DXA, QCT, and 3D-Shaper were expressed as percent change from pre-flight and evaluated by repeated measures ANOVA. A regression analysis of 1-year post-flight data compared the abilities of DXA (total hip areal BMD [aBMD]) and 3D-Shaper (trabecular volumetric BMD [Trab vBMD]) to predict persisting trabecular bone deficits as determined by QCT. RESULTS: Immediate postflight mean (SD) total hip aBMD was reduced by 3.9 (2.4)% with greater loss (p < 0.001) demonstrated by QCT and Shaper: 9.0 (7.2)% and 6.8 (4.5%), respectively. At 1-year post-flight, compared with QCT Trab vBMD change, R for the regression analysis of 3D-Shaper Trab vBMD change was 0.40 vs. 0.14 for DXA total hip aBMD. CONCLUSION: 3D-Shaper software predicts QCT-detected trabecular bone loss better than DXA and has the potential to serve as a screening tool for QCT-detection of trabecular bone loss.
Tortoli E, Riccio G, Mattii E
… +3 more, Ghezzi S, Giovannico G, Cioeta M
Osteoporos Int
· 2026 May · PMID 42154220
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BACKGROUND: High-intensity resistance and impact training (HiRIT) has emerged as a promising strategy to counteract bone loss and functional decline in peri- and postmenopausal women. However, heterogeneity in interventi...BACKGROUND: High-intensity resistance and impact training (HiRIT) has emerged as a promising strategy to counteract bone loss and functional decline in peri- and postmenopausal women. However, heterogeneity in intervention design and inadequate reporting limit reproducibility and clinical applicability. The Consensus on Exercise Reporting Template (CERT) provides a standardized framework for evaluating the completeness of exercise intervention reporting. Therefore, this review aimed to assess the reporting quality of HiRIT interventions using the CERT and to describe the key characteristics and training content of the implemented protocols. METHODS: A systematic review was conducted following PRISMA guidelines and registered in PROSPERO. Six electronic databases were searched up to June 2025. Original studies investigating HiRIT interventions in peri- or postmenopausal women were included. Reporting quality was assessed using the 19-item CERT checklist by two independent reviewers. RESULTS: Thirty-nine studies involving 3349 women (mean age 57.6 years) met the inclusion criteria. The mean CERT score was 14.3 out of 19, indicating moderate to good reporting quality. Exercise description, supervision, intervention structure, and equipment were consistently reported, whereas motivation strategies, home-based components, and detailed individualization were frequently omitted. Four progression-related CERT items were adequately reported in approximately two-thirds of the studies. Commonly prescribed exercises included the overhead press, squat, leg press, deadlift, and high-impact jumping tasks. CONCLUSIONS: HiRIT trials in peri- and postmenopausal women generally report core exercise components adequately, but important gaps remain in the reporting of progression, individualization, and behavioral support strategies. Improving the completeness and transparency of exercise reporting through consistent use of frameworks such as the CERT is essential to enhance reproducibility, facilitate clinical implementation, and optimize exercise prescription for bone health in this population.
Crabtree N, King B, Ayya M
… +2 more, Shaw N, Uday S
Osteoporos Int
· 2026 May · PMID 42149145
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BACKGROUND AND AIMS: Low bone mineral density (BMD) in children and young people (CYP) with anorexia nervosa (AN) is well recognized, yet the prevalence of osteoporosis remains unknown. This study investigates bone densi...BACKGROUND AND AIMS: Low bone mineral density (BMD) in children and young people (CYP) with anorexia nervosa (AN) is well recognized, yet the prevalence of osteoporosis remains unknown. This study investigates bone densitometry findings using dual energy X-ray absorptiometry (DXA) scan and peripheral quantitative computed tomography (pQCT) in girls with AN at initial referral, comparing outcomes by menstrual status and assessing osteoporosis prevalence. METHODS: A retrospective review included 264 girls with AN, aged 10.2-19.8 years, referred for initial DXA and pQCT scans at a tertiary pediatric bone densitometry service between March 2013 and October 2022. Data on anthropometry; self-reported fracture history; pubertal status (normal, delayed, irregular menstruation, secondary amenorrhea, or unclassified); and densitometry parameters were collected. Osteoporosis was defined per the International Society for Clinical Densitometry (ISCD) as the presence of vertebral fractures (VF) or both a clinically significant fracture history (≥ 2 long bone fractures by age 10 or ≥ 3 by age 19) and BMD Z-score ≤ -2.0. RESULTS: The cohort had a median age of 15.5 years, with 54.5% (n = 144) reporting secondary amenorrhea. Mean height SDS was 0.1 (1.0), while weight SDS [-0.8 (1.1)] and BMI SDS [-0.9 (1.1)] were significantly reduced (p < 0.001). Low BMD (lumbar spine bone mineral apparent density (BMAD) or total body less head BMD Z-score ≤ -2.0) was found in 18.9% (n = 50/264). Densitometry parameters were significantly lower than zero (p < 0.05), with greater deficits at trabecular-rich sites. BMD parameters, particularly total body less head BMD Z-score, were significantly better preserved in the secondary amenorrhea group compared to normal and delayed puberty groups (p < 0.05). pQCT showed reduced muscle (-2.4 [0.9]) and fat (-0.9 [1.0]) areas for height, with increased bone area for height (2.5 [1.4]). Long bone fractures were reported by 16.7% (n = 44), with 3% (n = 8) reporting two fractures. Mild single VFs were identified in 1% (n = 3), all meeting osteoporosis criteria due to VFs, with none having low BMD. No CYP met osteoporosis criteria based on fracture history and low BMD. CONCLUSIONS: Girls with AN exhibit significant bone density deficit at initial screening, particularly at trabecular sites, alongside reduced muscle and fat mass. However, osteoporosis as per current ISCD criteria is rare. Better skeletal health in the secondary amenorrhea group highlights the protective role of prior estrogen exposure.
Huang CF, Fang WH, Chen KH
… +57 more, Lin SY, Ho CJ, Hwang JS, Tai TW, Liu YF, Shih CA, Chen JF, Tu ST, Chan DC, Yang RS, Fu SH, Chen HY, Tsai KS, Cheng TT, Chen FP, Hung WC, Chang YF, Han DS, Chandran M, Bin AS, Lee JK, Yeap SS, Chung YS, Kim KK, Ebeling PR, Jaisamrarn U, Pandey D, Ferrari S, Yang TH, Charatcharoenwitthaya N, Taguchi A, Lekamwasam S, Van Nguyen T, Lewiecki EM, Saag KG, Tsai CC, Marín F, Mori S, Hwang KR, Li-Yu J, Carey JJ, Kendler D, Cheung CL, Huang HK, Kuptniratsaikul V, Chan WP, Chan SP, Ho-Pham LT, Hew FL, Shi H, Rhee Y, McCloskey E, Tanaka S, Hans D, Kanis JA, Chen CH, Wu CH
Osteoporos Int
· 2026 May · PMID 42142131
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UNLABELLED: Osteoporosis is a major and growing health concern in the Asia-Pacific region, y et it remains widely underdiagnosed and undertreated due to limited access to dual-energy X-ray absorptiometry (DXA) in many ar...UNLABELLED: Osteoporosis is a major and growing health concern in the Asia-Pacific region, y et it remains widely underdiagnosed and undertreated due to limited access to dual-energy X-ray absorptiometry (DXA) in many areas. Artificial intelligence (AI) offers new opportunities to improve osteoporosis screening and management, but unvalidated tools pose risks of inconsistent care. This consensus was developed to provide regionally harmonized guidance on the safe, effective, and equitable use of AI in osteoporosis care. PURPOSE: The aim of this work was to establish expert consensus recommendations on the role of AI in osteoporosis screening and management in the Asia-Pacific region. Key objectives were to define appropriate applications of AI (e.g., imaging-based bone assessment and fracture risk prediction) and specify minimum standards for validation and reporting, addressing region-specific implementation challenges and ensuring that AI use aligns with clinical guidelines and ethical principles. METHODS: This consensus was developed through multidisciplinary collaboration among experts across the Asia-Pacific region. Each participant reviewed draft statements, contributed feedback during virtual meetings, and provided insights based on clinical experience and current evidence. Consensus was reached iteratively until full agreement was achieved for all statements. The process integrated global best practices and regional adaptations, drawing from peer-reviewed studies, international AI guidelines, and local fracture registry data. The final recommendations emphasize the validation, transparency, and ethical implementation of AI within regional healthcare systems, ensuring compatibility with local regulations. Ultimately, twelve consensus statements were established to guide the responsible use of AI for osteoporosis screening and management in the Asia-Pacific region. RESULTS: The panel produced 12 consensus statements covering the role of AI as an adjunct for opportunistic osteoporosis screening rather than a diagnostic tool, requirements for imaging quality and AI model transparency, standards for validation and performance reporting, integration of AI with clinical risk stratification, demonstration of clinical utility in real-world settings, adherence to data protection laws and ethical AI principles, training of clinicians in AI use, strategies for implementation and monitoring (including post-market surveillance and feedback loops), and recognition of technical, clinical, and equity limitations of AI. All 12 statements give extensive recommendations for using AI to improve osteoporosis management while ensuring patient safety, accuracy, and equity. CONCLUSION: This first Asia-Pacific consensus on AI in osteoporosis concludes that AI, when appropriately validated and implemented, can help bridge the osteoporosis care gap by identifying high-risk patients who would otherwise remain undiagnosed, thus facilitating earlier intervention. It emphasizes that AI should complement-not replace-standard diagnostic methods and clinical judgment. The guidance emphasizes validation, transparency, and ethical oversight to facilitate early intervention while minimizing risks associated with unvalidated or premature AI adoption.
Lorentzon M, Wåhlstrand V, Alvén J
… +2 more, Häggström I, Johansson L
Osteoporos Int
· 2026 May · PMID 42118239
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UNLABELLED: XVFA is an AI-based method for identifying vertebral fractures on DXA images. In 423 women followed for 8 years, vertebral fractures identified by XVFA or manual assessment were associated with a twofold incr...UNLABELLED: XVFA is an AI-based method for identifying vertebral fractures on DXA images. In 423 women followed for 8 years, vertebral fractures identified by XVFA or manual assessment were associated with a twofold increased risk of incident fractures. XVFA predicted fracture risk comparably to manual assessment, supporting automated vertebral fracture detection. PURPOSE: Vertebral fractures (VFs), identified by vertebral fracture assessment (VFA) using dual-energy X-ray absorptiometry (DXA), predict incident fractures independently of clinical risk factors (CRFs) and bone mineral density (BMD). Most VFs remain clinically unrecognized. This study evaluated whether VFs identified using a deep learning-based method on lateral DXA images predict incident fractures comparably to manual VFA. METHODS: Associations between prevalent VFs and incident fractures were investigated in 423 women from the population-based SUPERB study who were not included in development of the explainable deep learning model (XVFA). Vertebrae were classified by manual VFA and XVFA. Incident fractures were X-ray verified. Cox proportional hazards models assessed fracture risk adjusted for CRFs and femoral neck (FN) BMD. RESULTS: Manual VFA reading and XVFA were used on baseline lateral images and classified 4563 and 5532 vertebrae, respectively, with numerical differences partly reflecting image quality limitations. VFs were identified in 102 women by manual VFA and 187 by XVFA. During 8 years of follow-up, incident fractures occurred in 48% of women with manual VFA VFs and 43% with XVFA VFs, vs 20% and 16% of women without VFs. Women with VFs had a higher fracture risk whether identified manually (HR 2.04; 95% CI, 1.35-3.07) or by XVFA (HR 2.32; 95% CI, 1.55-3.48), compared with women without VFs. Results remained significant after adjustment for CRFs and FN BMD. CONCLUSION: Automated XVFA predicted incident fractures similarly to manual assessment. These findings support the clinical utility of deep learning-based VF detection, which may enhance fracture risk assessment and management in routine practice.
Lynch LK, Kamanda-Kosseh M, Agarwal S
… +8 more, Shane E, Shiau S, Douglas J, El-Najjar D, Colon I, Del Orbe M, Bucovsky M, Cohen A
Osteoporos Int
· 2026 May · PMID 42113234
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UNLABELLED: This observational study of teriparatide-treated PLO documents a substantial effect of postpartum treatment timing on BMD response. Women who initiated teriparatide < 12 months (M) postpartum had two-threefol...UNLABELLED: This observational study of teriparatide-treated PLO documents a substantial effect of postpartum treatment timing on BMD response. Women who initiated teriparatide < 12 months (M) postpartum had two-threefold larger BMD increases than those initiating teriparatide ≥ 12M postpartum. This study provides important data to inform treatment response expectations in clinical care of teriparatide-treated PLO. PURPOSE: Pregnancy- and lactation-associated osteoporosis (PLO) describes an early-onset osteoporosis presentation with low- or no-trauma fractures associated with pregnancy/lactation; BMD at presentation is often extremely low. PLO fractures occur in the context of skeletal demineralization associated with pregnancy/lactation; natural BMD recovery is expected postpartum/postweaning, but BMD often remains quite low. Optimal management for PLO is uncertain. Teriparatide is the most common medication investigated. Observational studies document larger average BMD increases on teriparatide versus natural recovery-but individual response varies. Since treatment may overlap with the skeletally dynamic postweaning recovery period, we hypothesized that postpartum treatment timing would affect BMD response to teriparatide. METHOD: Within our PLO Registry, BMD was assessed at baseline, 6M, and 12M in 31 women with PLO who initiated teriparatide either < 12M postpartum (EarlyRx, n = 10, initiation 7 ± 3 M postpartum) or ≥ 12M postpartum (DelayedRx, n = 21, initiation 36 ± 29 M postpartum). Groups were similar in terms of age, BMI, parity, number of fractures, and breastfeeding duration. RESULTS: As expected, based on known postpartum bone physiology, baseline BMD was lower in EarlyRx vs. DelayedRx. Teriparatide was associated with significant BMD increases in both timing groups-but response differed substantially. Increases at 12M in the EarlyRx group (LS:+ 21 ± 12%, TH:+ 9 ± 6%, and FN:+ 7 ± 6%, all p < 0.01) were two-threefold larger than the DelayedRx group (LS:+ 8 ± 5%, TH:+ 4 ± 4%, and FN:+ 2 ± 3%, all p < 0.05). This effect was reproduced after controlling for baseline BMD. CONCLUSION: These data highlight the complexity of assessing treatment response in the context of postpartum bone physiology and can inform treatment response expectations for women with PLO.