Denosumab for osteoporotic fracture in a dialysis patient with non-low bone turnover

Question

A 76-year-old woman with ESRD is seen during dialysis rounds. She has been treated with in-center HD via a left upper extremity arteriovenous fistula for 3 years. A recent fall resulted in fracture of her hip, which was surgically repaired. Her home medications include cholecalciferol, cinacalcet, sevelamer, and calcitriol. Bone densitometry shows a T-score of -2.7. Laboratory data: PTH 614 pg/mL (reference 130–585, dialysis patients); alkaline phosphatase 113 U/L (30–120); 25-hydroxyvitamin D 32 ng/mL (30–60); phosphorus 4.2 mg/dL (3.0–4.5); calcium 8.7 mg/dL (8.6–10.2); albumin 3.4 g/dL (3.5–5.5). Which ONE of the following is the MOST appropriate next step in management?

Accepted Answer

B. Denosumab — This patient with osteoporosis and a history of fracture should be treated with the antiresorptive agent denosumab.

Bone densitometry, also referred to as dual energy x-ray absorptiometry (DEXA) scanning, is used to assess bone health and fracture risk. The result is reported as a T-score, which compares the bone density in the patient to that of a healthy 30-year-old of the same sex. A T-score of <-2.5 establishes the diagnosis of osteoporosis. Renal osteodystrophy affects bone quality and strength through multiple mechanisms and may be superimposed on low bone mineral density, contributing to fracture risk. Identification of the most appropriate therapy for patients with ESRD at high fracture risk requires categorization of the renal osteodystrophy component as low turnover, high turnover, or normal, based on the rate and quality of remodeling of bone that should normally occur. Although bone biopsy is the gold standard test to properly categorize patients, it is cumbersome, invasive, and expensive, and many centers lack the necessary expertise and experience to provide this diagnostic procedure. In the absence of bone biopsy, alkaline phosphatase and PTH levels well above normal suggest high bone turnover, whereas low or low-normal levels suggest low bone turnover, sometimes referred to as adynamic bone disease. Patients with osteoporosis and high turnover are candidates for antiresorptive therapy such as denosumab. Denosumab is a monoclonal antibody against the receptor activator of nuclear factor κB ligand (RANKL), which reduces bone turnover by inhibiting osteoclast development and proliferation. Denosumab is given as a subcutaneous injection every 6 months. Hypocalcemia is a frequent side effect in patients with CKD, especially those receiving dialysis, in whom hypocalcemia develops in more than one-third of cases. Treatment with calcium and vitamin D preparations and close monitoring are necessary. Bisphosphonates, such as alendronate, are also antiresorptive, but their use for osteoporosis in ESRD is currently contraindicated.

Etelcalcetide is an IV formulation of a calcimimetic agent similar to cinacalcet, which this patient is already prescribed. Although etelcalcetide may be more effective at lowering the PTH level than cinacalcet if oral absorption is limited, it would not address the underlying osteoporosis. Surgical parathyroidectomy could be performed to address severe hyperparathyroidism in cases refractory to calcimimetic therapy but also would not address the osteoporosis present in this patient, and this patient's PTH is only modestly above target. Additionally, the alkaline phosphatase is normal, suggesting that bone turnover may be overestimated by PTH in this patient.

Denosumab for osteoporotic fracture in a dialysis patient with non-low bone turnover

Explanation

Why each option

More CKD Bone Disease questions

Browse other topics