Teriparatide in postmenopausal women with osteoporosis and mild or moderate renal impairment.

Introduction: The prevalence of both osteoporosis and renal impairment increases with age.
Methods: Using data from the Fracture Prevention Trial, the safety and efficacy of teriparatide [rhPTH(1-34)] in postmenopausal women with osteoporosis and renal impairment were explored. Patients were required to have serum creatinine concentrations < or =2.0 mg/dl and normal serum parathyroid hormone (PTH) concentrations and were randomized to receive daily subcutaneous injections of placebo or teriparatide 20 or 40 mcg/day. Glomerular filtration rate (GFR) was estimated using the Cockcroft-Gault equation. Patients were defined from baseline assessments to have normal (GFR > or =80 ml/min), mildly impaired (GFR 50-79 ml/min), or moderately impaired (GFR 30-49 ml/min) renal function for bone mineral density (BMD) and amino-terminal extension peptide of procollagen type 1 (PINP) analyses, and normal (GFR > or =80 ml/min) or impaired (GFR <80 ml/min) renal function for fracture analyses.
Results and Conclusions: Compared with patients with normal renal function, patients with renal impairment were older, shorter, weighed less, had been postmenopausal longer, and had lower baseline lumbar spine and femoral neck BMD. Compared with placebo, teriparatide significantly increased PINP and lumbar spine and femoral neck BMD within each renal function subgroup, and there was no evidence that these increases were altered by renal insufficiency (each treatment-by-subgroup interaction p>0.05). Similarly, teriparatide-mediated vertebral and nonvertebral fracture risk reductions were similar and did not differ significantly between patients with normal or impaired renal function (treatment-by-subgroup interactions p>0.05). The incidences of treatment-emergent and renal-related adverse events were consistent across treatment assignment in the normal, mildly impaired, and moderately impaired renal function subgroups. Teriparatide induced changes in mean GFR were unaffected by baseline renal function (treatment-by-renal function interaction p>0.05 for normal, mildly impaired, or moderately impaired subgroups). Patients in all renal function categories treated with teriparatide 20 or 40 mcg had an increased incidence of 4-6-h postdose serum calcium >10.6 mg/dl (the upper limit of normal) versus placebo; however, teriparatide 20 mcg/day was not associated with significantly increased incidence of 4-6-h postdose serum calcium >11 mg/dl in any renal function category. Teriparatide therapy was associated with increased incidence of elevated uric acid, with the incidences being highest in patients with moderately impaired renal function and in those receiving teriparatide 40 mcg/day. Even so, adverse event data did not suggest an increased incidence of gout or arthralgia or of nephrolithiasis events in teriparatide-treated patients with normal, mild, or moderate renal impairment.