<![CDATA[Postmenopausal osteoporosis is a systemic skeletal disorder characterized by reduced bone mass and microarchitectural deterioration of bone tissue, leading to increased fragility fracture risk. This literature review aimed to comprehensively compare two primary antiresorptive therapy classes bisphosphonates and denosumab across pharmacological mechanisms, clinical efficacy, safety profiles, and patient adherence. A systematic literature search was conducted using PubMed, Google Scholar, and SciSpace databases, restricted to peer-reviewed publications from 2019 to 2026, including randomized controlled trials, meta-analyses, and real-world evidence studies. Bisphosphonates act by inhibiting farnesyl pyrophosphate synthase (FPPS) in the mevalonate pathway, inducing osteoclast apoptosis, whereas denosumab inhibits RANKL, mimicking the physiological function of osteoprotegerin. Evidence demonstrates that denosumab produces superior bone mineral density (BMD) gains at the lumbar spine and total hip, alongside higher real-world treatment persistence rates. Within Indonesia's National Health Insurance (JKN/BPJS Kesehatan) system, bisphosphonates risedronate, alendronate, and zoledronic acid are listed in the National Formulary (Fornas KMK 2197/2023) and fully reimbursed, whereas denosumab (Prolia®, Xgeva®, and biosimilar Corora® approved by BPOM in April 2024) has not yet been included. Both drug classes carry rare but serious risks of medication-related osteonecrosis of the jaw (MRONJ) and atypical femoral fracture (AFF). It is concluded that bisphosphonates remain the effective and affordable first-line therapy within the BPJS framework, while denosumab represents a valuable alternative for patients with bisphosphonate intolerance or inadequate treatment response.]]>
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