From the Guidelines
For preventing vertebral fractures in osteoporosis, bisphosphonates, such as alendronate or zoledronic acid, and denosumab are the most effective treatment options, as they have been shown to reduce the risk of vertebral fractures in both men and women with osteoporosis 1. The choice of treatment should be based on individual patient factors, including fracture risk, comorbidities, cost, and preference for administration route.
- Bisphosphonates, such as alendronate (70mg weekly) or zoledronic acid (5mg IV annually), are generally considered first-line treatment for preventing vertebral fractures in osteoporosis, as they have been shown to reduce the risk of vertebral fractures in both men and women with osteoporosis 1.
- Denosumab (60mg subcutaneous injection every 6 months) is another excellent choice, especially for patients with renal impairment where bisphosphonates may be contraindicated, as it has been shown to reduce the risk of vertebral fractures in patients with osteoporosis 1.
- For high-risk patients with severe osteoporosis or previous fractures, anabolic agents like teriparatide (20mcg daily subcutaneous injection for up to 24 months) or romosozumab (210mg monthly subcutaneous injection for 12 months) may be more effective as they actually build new bone rather than just preventing bone loss. Treatment should be accompanied by adequate calcium (1000-1200mg daily) and vitamin D (800-1000 IU daily) supplementation, as vitamin D deficiency is endemic worldwide and supplementation has been associated with a 15%–20% reduction in non-vertebral fractures 1. The medications work through different mechanisms, including:
- Bisphosphonates, which inhibit bone resorption by osteoclasts
- Denosumab, which blocks osteoclast formation
- Anabolic agents, which stimulate osteoblasts to build new bone tissue, all resulting in increased bone mineral density and reduced fracture risk. It is essential to consider the potential harms of treatment, including:
- Bisphosphonates, which are associated with mild gastrointestinal symptoms, atypical subtrochanteric fractures, and osteonecrosis of the jaw
- Denosumab, which is associated with increased risk for infection and rash or eczema
- Anabolic agents, which may have potential risks, such as hypercalcemia and hypercalciuria.
From the FDA Drug Label
The primary efficacy variable was the incidence of new morphometric (radiologically-diagnosed) vertebral fractures at 3 years. Vertebral fractures were diagnosed based on lateral spine radiographs (T4-L4) using a semiquantitative scoring method. Prolia significantly reduced the incidence of new morphometric vertebral fractures at 1,2, and 3 years (p < 0.0001), as shown in Table 3. The incidence of new vertebral fractures at year 3 was 7.2% in the placebo-treated women compared to 2.3% for the Prolia-treated women. The absolute risk reduction was 4.8% and relative risk reduction was 68% for new morphometric vertebral fractures at year 3.
Denosumab (Prolia) is the most effective osteoporosis treatment for preventing vertebral fractures, with a 68% relative risk reduction and 4.8% absolute risk reduction in new morphometric vertebral fractures at 3 years, as demonstrated in a 3-year, randomized, double-blind, placebo-controlled trial 2.
Alendronate sodium reduced the percentage of women experiencing at least one new radiographic vertebral fracture from 15.0% to 7.9% (47% relative risk reduction, p<0.001); in the Four-Year Study of FIT, the percentage was reduced from 3.8% to 2.1% (44% relative risk reduction, p=0.001); and in the combined U.S. /Multinational studies, from 6.2% to 3.2% (48% relative risk reduction, p=0.034).
In comparison, alendronate sodium reduced the incidence of radiographic vertebral fractures by 47% in the Three-Year Study of FIT and 44% in the Four-Year Study of FIT 3.
Key points:
- Denosumab (Prolia) has a higher relative risk reduction (68%) compared to alendronate sodium (47% and 44%).
- Denosumab (Prolia) has a higher absolute risk reduction (4.8%) compared to alendronate sodium (2.3% and 1.7%).
From the Research
Osteoporosis Treatment Options
The most effective osteoporosis treatment for preventing vertebral fractures is a topic of ongoing research. Several studies have investigated the efficacy of different treatments in reducing the risk of vertebral fractures.
Bisphosphonates
- Bisphosphonates, such as alendronate, risedronate, ibandronate, and zoledronic acid, are currently the most widely used osteoporosis medications 4, 5, 6, 7.
- These drugs increase bone mineral density (BMD) and reduce the risk of vertebral fractures by 40-70% 4.
- Zoledronic acid has been shown to be the most effective in preventing vertebral fracture, nonvertebral fracture, and any fracture 5.
- Alendronate and zoledronic acid have also been shown to be effective in preventing hip fractures 5, 7.
Anabolic Therapy
- Anabolic therapy with teriparatide has been demonstrated to be superior to the bisphosphonate risedronate in preventing vertebral and clinical fractures in postmenopausal women with vertebral fracture 4.
- Treatment with the sclerostin antibody romosozumab increases BMD more profoundly and rapidly than alendronate and is also superior to alendronate in reducing the risk of vertebral and nonvertebral fracture in postmenopausal women with osteoporosis 4.
Combination Therapy
- For patients with severe osteoporosis and high fracture risk, bisphosphonates alone are unlikely to be able to provide long-term protection against fracture and restore BMD 4.
- Sequential treatment, starting with a bone-building drug (e.g. teriparatide), followed by an antiresorptive, may provide better long-term fracture prevention 4.
Other Treatment Options
- Hormone therapy reduces fracture risk, but the benefits may not outweigh the reported risks 8.
- Raloxifene has been shown to lower the incidence of vertebral fractures in women with osteoporosis 8.
- Salmon calcitonin is reserved for use in patients who cannot tolerate bisphosphonates or hormone therapy 8.