Background Prostate cancer (PCa) patients are at increased fracture risk due to the need for androgen deprivation therapy (ADT) and progressive bone metastases. Previous meta-analyses of randomised controlled trials suggest that androgen receptor pathway inhibitors (ARPIs) increase fracture risk. Objective We assessed the impact of abiraterone-based treatment intensification on fracture-related hospitalisation (FRH) within the STAMPEDE trial platform. Design, setting and participants We performed a secondary analysis of two STAMPEDE trials in patients with high-risk non-metastatic (M0) or metastatic (M1) disease. Interventions Patients were allocated to either standard of care (SOC) or SOC plus abiraterone with prednisolone (AAP) or, in a later comparison, SOC+AAP with enzalutamide (Enza). Outcome measurements and statistical analysis A prespecified coding framework within Hospital Episode Statistics (HES) identified FRHs. Flexible parametric competing-risk models estimated 5-year cumulative incidence of FRH and sub-distribution hazard ratios (SDHR), with death as a competing risk. Outcome measurements and statistical analysis Between Nov 2011 and Mar 2016, 3893 patients were randomised to the STAMPEDE AAP±Enza trials. Linked HES data were available for 3102 patients in England. In M1 disease, 5-year FRH incidence was significantly lower with SOC + AAP than SOC alone (22% vs 30%; SDHR 0.77, 95%CI 0.59-0.99; p = 0.04) and with SOC + AAP + Enza than SOC alone (28% vs 38%; SDHR 0.69, 95%CI 0.54-0.88; p = 0.002). No significant difference was observed in M0 patients. Limitations include potential under-estimation of total fracture burden by exclusion of non-hospitalised fractures, lack of baseline assessment of fracture risk including bone mineral density, and longitudinal use of bone-protective therapy. Conclusions Abiraterone-based treatment intensification did not increase FRH compared to SOC alone. In M1 disease, abiraterone reduced rather than augmented fracture risk, most plausibly reflecting improved metastatic bone disease control.

FRAXplus complements the fracture risk assessment tool (FRAX) by incorporating additional risk factors to adjust 10-yr probabilities of major osteoporotic and hip fractures. We aimed to identify which adjustments most strongly influence fracture risk estimates and how they affect risk classification and treatment recommendations in Switzerland. We analyzed data from the Swiss Osteoporosis Registry (2015-2023), which captures all standard FRAX variables plus lumbar spine (LS) BMD, trabecular bone score (TBS), fall history in the previous year, oral glucocorticoid dosages, and the location and recency of prior fractures. Data on hip axis length and duration of type 2 diabetes were not available. A total of 28 708 individuals (88% women; mean age 65.8 ± 11.4 yr) were included, with a median 10-yr probabilities for major osteoporotic fracture (MOF) of 16% (interquartile range [IQR]: 9-24) using standard FRAX and 18% [IQR: 11-28] with FRAXplus adjustments. Most individuals (72%) had higher probabilities with FRAXplus (mean absolute increase: +4.8%), while 27% had lower probabilities (mean absolute decrease: -1.0%). TBS and LS minus FN T-score (LS - FN) influenced nearly all risk estimates, but differences between FRAX and FRAXplus were generally modest. At the individual level, ≥1 fall and recent vertebral or hip fractures produced the largest differences. Applying FRAXplus with Swiss intervention thresholds led to an upward reclassification in 16% of MOF estimates and a downward reclassification in 1%. In summary, FRAXplus adjustments significantly alter fracture risk estimates for most individuals. While LS BMD and TBS affect most probabilities, falls and recent vertebral or hip fractures have the largest absolute impact at the individual level, leading to clinically relevant changes in treatment recommendations according to Swiss guidelines.

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.

BACKGROUND:Osteoporosis increases fracture risk in older adults and is associated with impaired health-related quality of life (HRQoL). Osteoporosis-specific HRQoL instruments are widely used, but their measurement performance in older populations has not been comprehensively synthesised. OBJECTIVE:To systematically identify and synthesise development and validation studies of osteoporosis-specific HRQoL instruments for older adults, and to appraise their measurement properties using COSMIN criteria and a modified GRADE approach to inform instrument selection for clinical trials, routine care, and research. DESIGN:Systematic review. SETTING:Community-dwelling; Long-term care facility; Primary care facility. SUBJECTS:Older persons aged 60 years or over. METHODS:We searched Medline (Ovid), Embase, PsycINFO (Ovid), and AMED (Ovid) from inception to August 2024. We extracted and appraised evidence for COSMIN-defined measurement properties: content validity, structural validity, internal consistency, cross-cultural validity or measurement invariance, reliability, measurement error, criterion validity, hypothesis testing for construct validity, and responsiveness. Methodological quality was assessed using the COSMIN Risk of Bias checklist, measurement properties were rated against COSMIN criteria for good measurement properties, and certainty of evidence was graded using a modified GRADE approach. RESULTS:Forty-three studies reported the development and/or validation of nine osteoporosis-specific HRQoL instruments; language and version adaptations resulted in 15 instrument variants. Content validity was the most prominent limitation: only OPTQoL and the English Mini-OQLQ demonstrated sufficient evidence for multiple content validity components, while most widely used instruments lacked adequate evidence on item relevance, comprehensiveness, or comprehensibility. Evidence for internal structure was limited, with structural validity sufficient for ECOS-16 and QoLOS-NVFX, insufficient for QUALEFFO-41, and indeterminate for most other instruments. Cross-cultural validity and measurement invariance were almost entirely unexamined. By contrast, reliability and hypothesis testing for construct validity were more consistently supported, often with moderate-to-high certainty. Measurement error, interpretability, and responsiveness were poorly reported across instruments. CONCLUSIONS:The evidence base supports purpose-driven selection of osteoporosis-specific HRQoL instruments rather than a single preferred instrument. Across included studies, ECOS-16 shows the most consistently supported measurement properties in older adults for longitudinal assessment, although important evidence gaps remain (notably measurement error and cross-cultural validity). When brevity is the primary feasibility constraint in routine care, the Mini-OQLQ may be considered; however, evidence for responsiveness is limited.

Pregnancy- and lactation-associated osteoporosis (PLO) is a syndrome characterized by fragility fractures (most commonly vertebral, often multiple) occurring in late pregnancy or the early postpartum period. This position statement summarizes the current knowledge of PLO, and the recommended procedure for assessment, diagnosis and treatment based on a review of published evidence. As PLO is a rare condition, controlled, comparative clinical studies are limited. Individual studies were reviewed, focusing on design, size, follow-up, evaluation of safety, and factors that impact PLO outcomes. Diagnosis of PLO should include a detailed clinical examination, a review of medical and treatment history, and laboratory tests to rule out secondary osteoporosis. Imaging techniques can be used to inform the appropriate treatment pathway, which will depend on whether the patient is antepartum or postpartum. Management of PLO and fractures includes calcium/vitamin D intake/supplementation, considering stopping breastfeeding, and analgesia, if necessary. Treatment with bone-specific agents should be evaluated on an individual basis to reduce subsequent fracture risk, noting that their use in PLO patients is off label. If pharmacological treatments are used, they must be given alongside effective contraceptive measures. Bisphosphonates can pass the placental barrier and are detectable in bone for years, so adverse effects on future pregnancies, although not yet reported, cannot be excluded. Preferred treatment options are teriparatide/abaloparatide or romosozumab. Second-choice treatments are denosumab followed by bisphosphonates or bisphosphonates alone. This position statement includes a pragmatic approach for identifying women with PLO and suggests developing an individualized treatment plan that might include pharmaceutical intervention.

This expert position statement reframes arthroplasty and spinal fusion complications under the unified endpoint of implant fixation failure, defined as loss of mechanical integrity of the bone–implant unit over time. It synthesizes mechanistic and clinical evidence and provides evidence-informed recommendations for peri-operative bone health optimization. Osteoporosis is traditionally conceptualized as causing fragility fractures. However, compromised bone quality also affects the integrity of bone–implant constructs, influencing whether implants maintain fixation, interfaces remain stable, and fusion constructs consolidate. To synthesize mechanistic, translational, and clinical evidence on how osteoporosis and osteoporosis pharmacotherapies influence implant fixation failure across arthroplasty and spinal fusion, and to provide evidence-informed clinical recommendations for peri-operative bone health assessment and optimization within a unified construct-level framework. A position statement was developed following a structured literature search. Evidence was synthesized narratively by defining implant fixation failure as a construct-level outcome encompassing periprosthetic fracture, loosening, subsidence, pseudarthrosis, and junctional failure. Recommendations were categorized by strength (strong or conditional) and certainty of evidence (high, moderate, or low). Low bone mineral density (BMD) is associated with implant fixation failure across arthroplasty and spinal fusion. In arthroplasty, randomized trials demonstrate preservation of periprosthetic BMD with bisphosphonates, while registry analyses suggest improved implant survival. In spinal fusion, antiresorptive and anabolic therapies influence fixation-related parameters, with anabolic agents showing the most consistent evidence for enhanced fusion mass and earlier union. Much of the literature relies on radiographic or biomechanical endpoints rather than definitive outcomes. Viewing arthroplasty and spinal fusion complications through a shared construct-level perspective provides a coherent link between osteoporosis and reconstructive durability. Systematic peri-operative bone health optimization may improve construct longevity, although more definitive outcome-driven trials are needed. Closer integration between orthopedic surgeons and osteoporosis specialists will be central to advancing peri-operative bone health care.

We developed a revised FRAX® model for Sweden, derived from recent incidence data on fractures, mortality, and origin of birth, and defined age-dependent intervention thresholds. Since the development of the Swedish FRAX model in 2008, fracture incidence patterns have changed. The primary aim of this study was to develop a revised FRAX model, based on region of birth, and updated incidences for death and fracture for Sweden. A secondary aim was to define age-dependent intervention thresholds. Based on national registries, all persons from the age of 40 years living in Sweden between 2005 and 2021 were included. Yearly age- and sex-standardized incidences of hip fracture and major osteoporotic fracture (MOF) were calculated and presented per geographic region of birth. Hip fracture and MOF incidences from 2019 to 2021 were used to create a revised FRAX model for Sweden. Two models, one for Swedish/Nordic-born individuals and one for non-Nordic-born, were developed. The revised FRAX models were compared with the previous FRAX model. Age-specific intervention thresholds were calculated and presented. Compared with the previous FRAX model, the revised model yielded lower 10-year probabilities of both hip fracture and MOF in men and women. The non-Nordic models showed substantially lower probabilities across all age groups and sexes. Intervention thresholds for MOF without BMD ranged from a 10-year probability of 4.5

The International Osteoporosis Foundation (IOF) and the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) have proposed procollagen type I N propeptide (PINP) and β isomerized C-terminal telopeptide of type I collagen (β-CTX-I) as reference bone turnover markers (BTMs) for osteoporosis. This report examines the published literature since the 2011 IOF-IFCC position paper in order to determine the clinical potential of the reference BTMs and newer markers for the prediction of fracture risk and monitoring the treatment of osteoporosis. Evidence for the relationship between BTMs and subsequent fractures was gathered from prospective studies through literature review of the Medline database from years 2011 to May 2024. The impact of treatment on BTMs was also studied by examining publications in that period. Studies of the accuracy of BTMs in the assessment of bone turnover in the setting of advanced chronic kidney disease were also examined. Increased BTM concentrations are associated with higher fracture risk in postmenopausal women. PINP and β-CTX-I measured in blood are associated with fracture risk but their interaction with other risk factors has not been sufficiently studied limiting their incorporation into fracture risk algorithms. Treatment-induced changes in PINP and β-CTX-I account for a substantial proportion of fracture risk reduction and are useful for improving adherence; they are recommended for inclusion in studies to examine adherence in individual patients. However, total PINP (tPINP) and β-CTX-I may be elevated in CKD due to renal retention. Bone alkaline phosphatase (BALP), intact PINP (iPINP), and tartrate resistant acid phosphatase 5b (TRACP5b) show the most promise in discriminating high and low turnover bone diseases in patients with advanced CKD and for predicting fracture risk, monitoring treatment response, and assessing the risk of treatment-related complications. We re-affirm the use of serum/plasma tPINP and plasma β-CTX-I as reference BTMs with appropriate patient preparation and sample handling and measurement by standardized/harmonized assays in clinical studies to accumulate further data, and for monitoring treatment of osteoporosis in the setting of normal renal function in clinical practice. BALP and TRACP5b, measured by standardized assays, are recommended as reference BTMs for CKD-associated osteoporosis and should be included in observational and intervention studies to ascertain their utility for risk-evaluation, treatment initiation, and assessment of treatment response in CKD-associated osteoporosis.

FRAXplus® facilitates adjustment of FRAX® fracture probabilities for additional clinical risk factors. This study examined how FRAXplus adjustments affect the proportion of older Swedish women eligible for treatment at a major osteoporotic fracture (MOF) probability intervention threshold (IT) ≥ 26

Background: Women with hormone-responsive breast cancer who receive adjuvant endocrine treatment with aromatase inhibitors (AI) are known to be at higher fracture risk due to a marked increase in bone resorption. In 2017, several interdisciplinary cancer and bone societies involved in the management of women with AI-associated bone loss (AIBL) published a joint position statement comprising evidence-based recommendations and a practical management algorithm for the assessment of fracture risk and optimal treatment of this patient population. Patients and methods: In order to provide updated recommendations that reflect recent advances in the assessment and management of AIBL since publication of the 2017 joint position statement, a systematic literature review was undertaken to identify relevant studies for analysis, including systematic reviews and meta-analyses. Individual trials identified were assessed for their level of evidence based on design, size, follow-up, and evaluation of safety, as well as the impact of bone directed treatments on breast cancer outcomes. Results: New evidence was combined with the existing recommendations to provide an updated joint position statement regarding fracture risk assessment and implementation of bone-directed therapy. Conclusion: Current published literature, including recent clinical trial reports, systematic reviews and meta-analyses, continue to affirm the high risk of fractures in women with breast cancer who are receiving adjuvant AI treatment, a risk which has been observed to increase with the commonly used approach of extended duration AI therapy (>5 years). Risk factors for fracture and risk assessment in this patient population as well as the most suitable treatment modalities have been updated. Finally, the influence of bone protective treatments on breast cancer outcomes such as incidence of bone metastasis and breast cancer related overall survival have been included.

Osteoporosis is a major global public health problem with the associated bone fractures contributing significantly to both morbidity and mortality. In many countries, osteoporotic fractures will affect one in three women and one in five men over the age of 50. Similarly, diabetes, obesity, and metabolic syndrome (MetS) are among the leading public health problems due to their worldwide prevalence and burden on health budgets. Although seemingly disparate, metabolic disorders are known to affect bone health, and the interaction between fat and bone tissue is increasingly well understood. For example, it is now well established that diabetes mellitus (both type 1 and 2) is associated with fracture risk. In this narrative review, we focus on the potential link between MetS and bone health as expressed by bone mineral density and fracture risk. This narrative review demonstrates the association of MetS and its components with increased fracture risk, and also highlights the need for fracture risk assessment in patients with obesity and MetS.

Chronic kidney disease (CKD)-associated osteoporosis increases fracture risk, yet clinical guidance remains unclear. A survey of 89 Italian nephrologists revealed heterogeneous biomarker availability and varied treatment approaches. Denosumab was the preferred antiresorptive agent, while anabolic drugs were rarely used. Findings highlight progress in CKD-related bone health management despite existing uncertainties. CKD-associated osteoporosis comprises the skeletal effects of a complex mineral and bone disorder causing increased risks of fragility fractures (FF), cardiovascular events, and mortality. Existing clinical guidance about CKD-associated osteoporosis is vague, leading us to hypothesize that a treatment gap exists and that clinical practice is dependent on local availability of diagnostic tools. The aim of the current survey was to determine current attitudes and practices among Italian nephrologists regarding the evaluation and management of CKD-associated osteoporosis. An online survey was designed, consisting of 9 thematic groups with a set of 16 closed questions regarding the availability of biomarkers and BTMs at reference laboratories and their use for the diagnosis and treatment of CKD-associated osteoporosis in patients with different stages of CKD, including CKD stages G4-5 and dialysis patients. Results were compared to a previous survey on the use of BTMs from 2022. Eighty-nine Italian nephrologists participated in the survey, reporting that parathyroid hormone (PTH), alkaline phosphatase, and 25-hydroxy-vitamin D measurements were available in 92–100

Pain is the most common symptom of Paget’s disease of bone (PDB), but its underlying mechanisms are poorly understood. Notably, bone pain does not correlate well with metabolic activity or treatment response. This study aimed to assess whether sensory processing is altered in skin overlying Pagetic bone using quantitative sensory testing (QST). We conducted a cross-sectional study of 156 people with PDB attending secondary care referral centres in the UK. We conducted quantitative sensory testing of the skin overlying affected sites and compared the data with unaffected sites as a control. The modalities used were hot and cold rollers, pinprick, vibration and von-Frey filaments to test both spinothalamic and lemniscal pathways. There was a consistent trend for sensory perception to be increased over affected sites versus control sites in the study population. The differences were significant for vibration detection threshold (p = 0.009), pain threshold (p = 0.010) and both single and multiple pinprick testing methods (both p < 0.001). Subgroup analysis revealed similar trends when analysis was restricted to those with pain thought to be due to bone deformity or increased metabolic activity and those with and without musculoskeletal pain. Sensory processing is altered in skin overlying Pagetic bone, independent of current pain symptoms. We speculate that this may be due to abnormalities of bone shape, bone structure or metabolic abnormalities in the affected bone. The mechanisms are unclear but deserve further study.

The relationship between rheumatoid arthritis (RA) and fracture risk was estimated in an international meta-analysis of individual-level data from 29 prospective cohorts. RA was associated with an increased fracture risk in men and women, and these data will be used to update FRAX®. RA is a well-documented risk factor for subsequent fracture that is incorporated into the FRAX algorithm. The aim of this study was to evaluate, in an international meta-analysis, the association between rheumatoid arthritis and subsequent fracture risk and its relation to sex, age, duration of follow-up, and bone mineral density (BMD) with a view to updating FRAX. The resource comprised 1,909,896 men and women, aged 20–116 years, from 29 prospective cohorts in which the prevalence of RA was 3

Using data from a meta-analysis including 606,715 women, we found that the predictive value of a fall the past year for future hip fractures in women significantly decreases with age, resulting in a diminishing population attributable risk with increasing age.PurposeIn a recent meta-analysis of 40 cohorts, we demonstrated that a fall history in the past year was associated with an increased risk of hip fracture. An interaction between fall history and age was observed in women, with lower hazard ratios (HR) for older women. This study aimed to determine the population-attributable risk (PAR) for hip fracture due to increased fall risk in women of different ages.MethodsFall history associated attributable risk (AR, %) for hip fracture was calculated [100(1-1/relative risk (HR))] for women per age stratum, using previously calculated HRs. PAR (%) of hip fractures in the female population (>= 50 years) that could be prevented if the fall history-mediated risk increase could be eliminated was calculated as 100Pexp(HR-1)/[1 + Pexp(HR-1)] where Pexp was the exposed proportion of the population (i.e. the proportion with past falls).ResultsA total of 606,715 women included from 40 cohorts, with fall risk documented in the past year (fall history yes/no or 2 or more falls) and prospective information about hip fracture and death, were analysed. The proportion of fallers increased progressively with age from 24.6% at age 50-54 years to 45.5% at age 90-94 years. In contrast, the AR due to falls decreased, from 54.8% at age 50-54 years to 8.3% at age 90-94 years, and the PAR diminished with age, from 23.9% in women 50-54 years old to 3.9% in women 90-94 years old.ConclusionsAs falls become more common with age, their predictive value for future hip fractures in women significantly decreases. This suggests that the effectiveness of fall prevention strategies in reducing hip fractures is lower in older women, who are at higher risk for serious falls and hip fractures.

A surrogate FRAX® model for Mongolia has been constructed using age- and sex-specific hip fracture rates for mainland China and age- and sex-specific mortality rates from Mongolia. FRAX models are frequently requested for countries with little or no data on the incidence of hip fracture. In such circumstances, the development of a surrogate FRAX model is recommended based on country-specific mortality data but using fracture data from a country, usually within the region, where fracture rates are considered to be representative of the index country. This report describes the development and characteristics of a surrogate FRAX model for Mongolia. The FRAX model used the ethnic-specific incidence of hip fracture in mainland China, combined with the death risk for Mongolia in 2015–2019. Intervention thresholds were developed based on fracture probabilities equivalent to women with a prior fragility fracture, and their impact was assessed in a referral cohort comprising men at age 50 and above and postmenopausal women. The number of hip fractures in 2015 and 2050 was estimated based on United Nations’ predicted changes in population demography. The surrogate model gave similar hip fracture probabilities to estimates from China. Age-dependent intervention thresholds for a major osteoporotic fracture ranged from a 10-year probability of 2.4

Osteoporosis and osteoarthritis are key diseases of musculoskeletal ageing and are increasing in prevalence and burden with the progressively ageing population worldwide. These conditions are thus particularly common in 'the oldest old', and there are complexities of managing them within the context of extensive multimorbidity, physical and mental disability, and polypharmacy, the rates for all of which are high in this population. In this narrative review, we explore the epidemiology of osteoporosis and osteoarthritis in the oldest old before examining trials and real-world data relating to the pharmacological treatment of these diseases in older adults, including anti-resorptives and bone-forming agents in osteoporosis and symptomatic slow-acting drugs for osteoarthritis, paracetamol, and non-steroidal anti-inflammatory drugs in osteoarthritis, recognising that the oldest old are usually excluded from clinical trials. We then review the potential benefits of nutritional interventions and exercise therapy before highlighting the health economic benefits of interventions for osteoporosis and osteoarthritis. The high prevalence of risk factors for both disease and adverse events associated with treatment in the oldest old mean that careful attention must be paid to the potential benefits of intervention (including fracture risk reduction and improvements in osteoarthritis pain and function) versus the potential harms and adverse effects. Further direct evidence relating to such interventions is urgently needed from future research.

Parathyroid hormone (PTH) regulates bone homeostasis. Intermittent exposure to PTH results in bone formation being greater than bone resorption, and this effect has been harnessed through the development of agonists of the PTH and PTH-related protein type 1 receptor (PTH1R) to treat osteoporosis. Teriparatide, an analogue of the first 34 amino acids of PTH, and abaloparatide, which resembles PTH-related protein (PTHrP) in structure, are PTH1R agonists currently in clinical use. Both medications have been shown to increase bone mineral density at the lumbar spine, femoral neck and total hip. Randomized controlled trials with teriparatide or abaloparatide have also provided evidence of reduction in vertebral and non-vertebral fractures. The ACTIVE trial suggested slightly greater efficacy for major osteoporotic fractures (as an exploratory end point) for abaloparatide than for teriparatide. A similar potential superiority was suggested for hip fracture in a real-world, observational study. Side effects of these medications are usually transient, and although a risk of osteosarcoma was suggested by studies using murine models, no such risk has been observed in extensive human studies. Overall, both teriparatide and abaloparatide have demonstrated convincing clinical effectiveness and cost-effectiveness, with a reassuring safety profile. Potential differences in their effects on bone mineral density and their antifracture effects offer avenues for differentiation but require further validation in appropriately designed studies. This Review summarizes clinical effectiveness, health economics and safety data on the parathyroid hormone receptor agonists teriparatide and abaloparatide, discussing potential strategies and drug combinations to achieve best outcomes in patients with osteoporosis.