Stimulators of Bone Formation
Teriparatide is a recombinant protein of the 34 first amino acids of human PTH, an anabolic agent approved by the FDA for the treatment of postmenopausal osteoporosis. The pivotal fracture trial of teriparatide (dose 20 mcg/day or 40 mcg/day) included some women with an eGFR as low as 30 ml/min. Post-hoc analyses demonstrate that there was an increase in BMD in all subsets of CKD stage and fractures, but numbers were too small to reach statistical significance. There was no greater risk of nephrolithiasis and serum uric acid increased with no clinical consequence. Of note, there are also some case reports of teriparatide use in bone biopsy-confirmed adynamic bone disease demonstrating that the agent increases bone turnover and is well tolerated.
Romosozumab is an antisclerostin antibody. Sclerostin, an osteocyte-secreted glycoprotein, inhibits Wnt and bone morphogenic protein signaling pathways, which are promoters of bone formation. By inhibiting sclerostin, romosozumab could potentially stimulate bone formation. A phase 2, prospective study in postmenopausal women has shown benefits of romosozumab bone mineral density, as well as transitory increase in bone-formation markers and sustained decrease in a bone-resorption marker, in comparison to alendronate and teriparatide. The potential benefits of this drug include the nonrenal clearance, and the recent findings of increased bone expression and serum levels of sclerostin in CKD patients. If the current belief that sclerostin is increased in early CKD stages and could be associated with CKD-related bone resistance to PTH is correct, a new avenue for therapy of bone disease in CKD is being opened. However, although very promising, all these therapeutic agents should be tested in randomized clinical trials in CKD patients to demonstrate fracture risk reduction and safety.