Osteoporosis, a common systemic metabolic disease [1], is characterized by a decrease in bone density and bone mass, destruction of bone tissue microstructure, and increased bone fragility leading to fracture susceptibility [1]. Osteoporosis is sometimes referred to as a silent disease because bone loss occurs without signs or symptoms until fractures occur [2]. Estimated prevalence is over 200 million individuals globally [3], The worldwide prevalence is estimated at 18.3 %, higher in women (23.1 %) than men (11.7 %) [4], with 1 in 3 women and 1 in 5 men over 50 suffering osteoporotic fractures [3]. In Australia, the economic impact is substantial, with projected annual costs exceeding $3.82 billion, where fracture-related expenses account for 67 % of total costs [5]. The global burden and costs associated with osteoporotic fractures are significant [6].

The disease results from an imbalance in bone turnover, where bone resorption exceeds formation. Multiple factors [7] contribute to this imbalance, including age-related changes, hormonal deficiencies (particularly post-menopausal estrogen deficiency), genetic factors, nutritional status, lifestyle factors like smoking, and low physical activity. Secondary causes such as medications (e.g., glucocorticoids, proton pump inhibitors, antiepileptics) and medical conditions (e.g. hyperparathyroidism, thyroid disorders, chronic kidney disease) significantly influence disease development and progression.

Traditional treatment strategies primarily utilized antiresorptive agents and anabolic agents [8], with bisphosphonates being the most commonly prescribed antiresorptive [9]. While these medications effectively reduce fracture risk, their limitations include potential adverse effects with prolonged use [10] and reduced efficacy in severe osteoporosis. Conventional treatments include Selective Estrogen-Receptor Modulators (SERMs), bisphosphonates, parathyroid hormone analogs, and calcitonin [1]. The development of anabolic agents that promote bone formation has provided alternative options for high-risk patients [11]. Diagnosis commonly involves bone mineral density measurement using dual-energy X-ray absorptiometry (DXA) to generate a T-score, with osteoporosis defined by a T-score of −2.5 or lower according to WHO criteria [12]. Fracture risk assessment tools like FRAX incorporate clinical risk factors alongside BMD [13].

This review examines emerging therapeutic approaches in osteoporosis management, including recently approved medications, novel treatment modalities, and investigational therapeutic targets [14]. We assess the mechanisms of action, clinical trial outcomes, safety profiles, and practical implementation considerations. Additionally, we evaluate combination and sequential therapy strategies that may enhance patient outcomes.