ABSTRACT Background Osteoporosis (OP) is a common skeletal disorder characterized by decreased bone mass and increased fracture risk. Anabolic agents such as teriparatide (TP) and abaloparatide (ABL) have been introduced to stimulate bone formation and reduce fracture incidence. However, whether their use increases the risk of musculoskeletal and connective tissue disorders (MCTD) remains unclear. Research design and methods A retrospective, observational disproportionality analysis was conducted utilizing FAERS data from Q1 2004 to Q3 2023, where TP or ABL was identified as the primary suspect drug. Multiple data mining algorithms, including reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS), were employed to detect MCTD safety signals. Results A total of 366,747 TP-related and 422,377 ABL-related cases were identified, predominantly among female patients aged ≥45 years. The top specific AEs involved musculoskeletal, connective tissue, and administration site disorders. Comparative analysis revealed a higher frequency of AEs related to the nervous, cardiovascular, and gastrointestinal systems for ABL compared to TP. Both drugs exhibited strong signals for arthralgia, limb pain, back pain, muscle spasms, bone pain, muscle pain, and muscle weakness. Conclusion This FAERS-based data mining analysis highlighted potential MCTD risk profiles associated with TP and ABL treatment in osteoporosis patients, emphasizing the importance of monitoring and managing these AEs in clinical practice. The findings contribute to a deeper understanding of the safety profiles of these anabolic osteoporosis medications.