From the Guidelines
The best therapeutic option to decrease this patient's risk of future fractures is denosumab administered subcutaneously. This 75-year-old woman has osteoporosis, evidenced by her compression fracture and T-scores, and also has stage 4 chronic kidney disease (CKD) with a creatinine clearance of 21 mL/min. Denosumab is preferred in this case because it's not renally cleared and is safe for patients with severe renal impairment, as supported by the American College of Physicians guideline update from 2017 1. Bisphosphonates like alendronate are generally contraindicated in patients with creatinine clearance below 30-35 mL/min due to potential accumulation and nephrotoxicity.
Key Considerations
- Denosumab works by inhibiting RANK ligand, which reduces osteoclast formation and activity, thereby decreasing bone resorption and increasing bone density.
- The standard dosing is 60 mg subcutaneously every 6 months.
- Patients should continue calcium and vitamin D supplementation while on denosumab therapy.
- Common side effects include musculoskeletal pain, hypercholesterolemia, and skin infections.
- Rare but serious side effects include osteonecrosis of the jaw and atypical femur fractures, though these risks are outweighed by the benefits of fracture prevention in this high-risk patient with a history of fragility fracture.
Guideline Recommendations
The American College of Physicians recommends offering pharmacologic treatment with alendronate, risedronate, zoledronic acid, or denosumab to reduce the risk for hip and vertebral fractures in women who have known osteoporosis 1. However, given this patient's severe renal impairment, denosumab is the preferred option. The 2022 American College of Rheumatology guideline for the prevention and treatment of glucocorticoid-induced osteoporosis also conditionally recommends denosumab for patients at high or very high risk of fracture 1.
Patient-Specific Factors
This patient's stage 4 CKD and history of fragility fracture place her at high risk for future fractures, making denosumab the best therapeutic option to decrease her risk. The benefits of denosumab in preventing fractures outweigh the potential risks, especially considering her renal impairment and the contraindication of bisphosphonates in such cases.
From the FDA Drug Label
The efficacy and safety of once-daily teriparatide, median exposure of 19 months, were examined in a double-blind, multicenter, placebo-controlled clinical study of 1637 postmenopausal women with osteoporosis. Teriparatide, when taken with calcium and vitamin D and compared with calcium and vitamin D alone, reduced the risk of 1 or more new vertebral fractures from 14.3% of women in the placebo group to 5. 0% in the teriparatide group (444 of the 541 patients treated with 20 mcg once daily of teriparatide were included in this analysis). This difference was statistically significant (p <0.001); the absolute reduction in risk was 9. 3% and the relative reduction was 65%. Teriparatide was effective in reducing the risk for vertebral fractures regardless of age, baseline rate of bone turnover, or baseline BMD. New Nonvertebral Osteoporotic Fractures — Teriparatide significantly reduced the risk of any nonvertebral fracture from 5. 5% in the placebo group to 2.6% in the teriparatide group (p <0.05). The absolute reduction in risk was 2.9% and the relative reduction was 53%.
The best therapeutic option to decrease this patient's risk of future fractures is Teriparatide subcutaneously.
- Key benefits:
- Reduced risk of new vertebral fractures by 65%
- Reduced risk of nonvertebral fractures by 53%
- Increased bone mineral density (BMD) at the lumbar spine, femoral neck, total hip, and total body
- Study reference: 2
From the Research
Patient Profile
- The patient is a 75-year-old woman with a compression fracture of her tenth thoracic vertebra.
- Her medical history includes hypertension, hyperlipidemia, type 2 diabetes mellitus, gastroesophageal reflux disease, and stage 4 chronic kidney disease.
- Laboratory results show a calcium level of 8.9 mg/dL, albumin level of 3.6 g/dL, creatinine level of 2.3 mg/dL, and calculated creatinine clearance of 21 mL/min.
- The patient's DXA scan shows a T-score of -2.0 at the lumbar spine and -1.8 at the femoral neck.
Treatment Options
- The patient is currently taking calcium and vitamin D supplementation.
- The best therapeutic option to decrease the patient's risk of future fractures is denosumab subcutaneously, as it has been shown to improve bone mineral density and reduce bone turnover in patients with chronic kidney disease 3.
- Denosumab is also preferred in patients with impaired renal function, as it does not accumulate in the body and can be safely used in patients with stage 4 chronic kidney disease 4, 3.
- Other treatment options, such as alendronate and teriparatide, may also be effective, but denosumab has been shown to have a greater increase in bone mineral density and a lower risk of osteoporotic fractures 5, 6.
Key Considerations
- The patient's stage 4 chronic kidney disease requires careful consideration when selecting a treatment option.
- Denosumab-induced hypocalcemia is a potential risk, and the patient should be closely monitored for signs of hypocalcemia 3.
- The patient's calcium and vitamin D supplementation should be continued, and her kidney function should be closely monitored while on denosumab therapy.