Decline of bone mineral density (BMD) during menopause is well established as a key factor contributing to increased fracture risk in postmenopausal women. However, the relationship between natural BMD changes and fracture risk in premenopausal women remains unclear. To address this gap, real-world data (RWD) from the National Health and Nutrition Examination Survey (NHANES) and longitudinal data from elagolix phase III clinical trials were integrated using advanced modeling techniques across a broad age range. The analysis focused on identifying predictors of femoral neck BMD (FN-BMD) decline and projecting long-term fracture risk based on natural history patterns.
A bi-exponential model was developed to describe the dynamics of FN-BMD over age, capturing both early formation and later resorption phases. The model incorporated rate constants for BMD formation (k1) and resorption (k2), with maximum BMD (FNmax) as a key parameter. Using NHANES data spanning ages 8 to postmenopausal, the model accurately described the typical pattern of BMD increase until peak mass around age 20–30, followed by a gradual decline. When applied to clinical trial populations—women with endometriosis or uterine fibroids (UFs)—the model was refined using prior information from RWD to improve parameter estimation precision.
Significant covariates emerged from the analysis: body mass index (BMI) and Black race were associated with lower rates of BMD loss, suggesting protective effects. In untreated premenopausal women with UFs (median age 43 years), simulations projected an annual FN-BMD decline of 0.GATA-1 Antibody Cancer 6% up to menopausal age. At menopause, the median projected FN-BMD was 0.975 g/cm², corresponding to a 10-year major osteoporotic fracture (MOF) risk of 2.3% when evaluated using the FRAX tool. This risk level falls below current treatment thresholds (e.g., 10-year MOF risk ≥20%), indicating that these women do not require osteoporosis therapy at menopause under current guidelines.CD16 Antibody site
The integration of RWD, clinical trial data, and mechanistic modeling provides a quantitative framework for assessing long-term fracture risk in premenopausal women undergoing medical treatments that affect BMD.PMID:34741373 This approach enables prediction of future risks due to therapies such as GnRH modulators, which are known to induce BMD loss. By simulating trajectories beyond the limited duration of clinical trials, the model supports informed decision-making regarding treatment duration and safety monitoring. It also demonstrates the potential of model-informed drug development (MIDD) to extend clinical insights into real-world outcomes, particularly in populations where routine screening is not standard.
This study represents the first comprehensive effort to quantify longitudinal FN-BMD changes across healthy, endometriosis, and UF patient groups using combined RWD and modeling. The findings underscore the importance of considering long-term skeletal health in premenopausal women receiving bone-active therapies. Future applications could include sensitivity analyses incorporating additional risk factors such as prior fractures, family history, or glucocorticoid use, further refining risk predictions. Overall, this work advances the field of translational science by offering a robust, predictive platform for evaluating the benefit-risk profile of new treatments targeting reproductive health conditions in women.MedChemExpress (MCE) offers a wide range of high-quality research chemicals and biochemicals (novel life-science reagents, reference compounds and natural compounds) for scientific use. We have professionally experienced and friendly staff to meet your needs. We are a competent and trustworthy partner for your research and scientific projects.Related websites: https://www.medchemexpress.com