From the Guidelines
Bisphosphonates are the most effective medications for treating osteoporosis in treatment-naive patients, with a strong recommendation and high-certainty evidence.
Efficacy of Osteoporosis Medications
The efficacy of various osteoporosis medications in treatment-naive patients with osteoporosis is well-established, with bisphosphonates being the most effective, as recommended by the American College of Physicians (ACP) 1.
- Bisphosphonates, such as alendronate, risedronate, and zoledronic acid, have been shown to reduce the risk of vertebral and nonvertebral fractures in postmenopausal women and men with osteoporosis 1.
- Denosumab, a RANK ligand inhibitor, is recommended as a second-line treatment for postmenopausal women with primary osteoporosis who have contraindications to bisphosphonates 1.
- Romosozumab and teriparatide may be considered for females with primary osteoporosis at very high risk of fracture, although the evidence is less certain 1.
Benefits and Harms of Treatment
The benefits of osteoporosis medications, including reduction in fracture risk, must be weighed against the potential harms, such as:
- Bisphosphonates: mild upper GI symptoms, atypical subtrochanteric fractures, and osteonecrosis of the jaw 1.
- Denosumab: mild upper GI symptoms, rash or eczema, and increased risk of infection 1.
- Teriparatide: upper GI symptoms, renal issues, headaches, hypercalcemia, and hypercalciuria 1.
Treatment Selection and Adherence
Treatment selection should be individualized, taking into account the patient's baseline risk for fractures, comorbidities, and concomitant medications 1.
- Adherence to osteoporosis medications is crucial, and clinicians should discuss the importance of adherence with patients, monitoring bone turnover markers to identify non-adherence 1.
Clinical Practice Guidelines
The ACP recommends that clinicians use bisphosphonates as the initial pharmacologic treatment for primary osteoporosis, with denosumab as a second-line option 1.
- The American College of Physicians also provides guidelines for the treatment of low bone density or osteoporosis in men and women, including recommendations for pharmacologic treatment and monitoring 1.
- The evidence-based guideline for the management of osteoporosis in men supports the use of bisphosphonates or denosumab as first-line therapy, with oral bisphosphonates recommended as the initial treatment 1.
From the Research
Efficacy of Osteoporosis Medications
The efficacy of various osteoporosis medications in treatment-naive patients with osteoporosis has been evaluated in several studies.
- Teriparatide, risedronate, and etidronate have been associated with decreased vertebral fracture risk 2.
- Antiresorptive drugs, such as bisphosphonates and denosumab, have been shown to increase bone mineral density (BMD) and reduce the risk of vertebral, nonvertebral, and hip fractures in postmenopausal women with osteoporosis 3.
- Teriparatide has been demonstrated to be superior to risedronate in preventing vertebral and clinical fractures in postmenopausal women with vertebral fracture 3.
- Romosozumab has been shown to increase BMD more profoundly and rapidly than alendronate and is superior to alendronate in reducing the risk of vertebral and nonvertebral fracture in postmenopausal women with osteoporosis 3.
- A network meta-analysis of randomized controlled trials found that teriparatide had the lowest incidence of vertebral fracture, while ibandronate had the lowest incidence of non-vertebral fracture 4.
- Raloxifene and denosumab have been shown to increase BMD in the lumbar spine and total hip, respectively 4.
- A real-world study in Japan found that romosozumab increased BMD at the lumbar spine in treatment-naive patients, and that sequential therapy with denosumab, bisphosphonates, or teriparatide maintained BMD gains at all skeletal sites 5.
Comparison of Treatment Options
The various osteoporosis medications have different efficacy and safety profiles.
- Bisphosphonates, such as alendronate and risedronate, have been shown to increase BMD and reduce fracture risk, but have been associated with rare side effects such as osteonecrosis of the jaw 3, 6.
- Denosumab has been shown to increase BMD and reduce fracture risk, and has been associated with a lower risk of adverse events compared to bisphosphonates 3, 4.
- Teriparatide has been shown to be effective in preventing vertebral and clinical fractures, but has been associated with a higher risk of adverse events compared to bisphosphonates 2, 3.
- Romosozumab has been shown to increase BMD and reduce fracture risk, and has been associated with a lower risk of adverse events compared to bisphosphonates 3, 5.
Treatment Gap
Despite the availability of effective treatments, there is a significant treatment gap in osteoporosis, with many patients remaining undertreated or untreated 6.