Endocrine Abstracts

Osteoanabolics, i.e., agents that stimulate the osteoblast to form new bone, are the most efficacious among antiosteoporotic regimens and are considered as the spearhead of severe osteoporosis management. Currently available osteoanabolic agents can be divided into molecules that bind and stimulate the receptor type 1 of parathyroid hormone (PTH1R), teriparatide (TPTD) and abaloparatide (ABL), and monoclonal antibodies against sclerostin, with romosozumab (ROMO) to be the only representative of the class in clinical practice. Osteoanabolic agents increase BMD and bone strength while being more effective than antiresorptives in reducing fracture risk in postmenopausal women. Osteoanabolic agents typically serve as a second line therapy in case of antiresorptives’ failure. However, they could (and should) also be used as a first line treatment in patients at high fracture risk, given that they perform better when given in treatment-naïve patients and that in patients at very high/imminent fracture risk, a rapid fracture risk reduction is critical to prevent new fractures. Among osteoanabolics, ROMO was more effective than TPTD in increasing BMD in treatment-naïve women and in women previously treated with bisphosphonates but there is no direct comparison of the antifracture benefits of the two agents. In contrast, in a head-to-head comparative study ABL achieved greater BMD increases at the hip than TPTD and led to a greater reduction of major osteoporotic fractures but with no differences in vertebral or non-vertebral fracture risk. There is no direct comparison of ROMO with ABL at present. With PTH1R agonists, stimulation of bone formation is maintained for as long as their administration is continued, the increase of bone formation with ROMO seems to be transient, lasting only for the first few months of treatment, with suppressed bone formation for the remainder of therapy. ROMO might have an advantage over PTH1R agonists in patients with renal insufficiency as well as in patients with hypercalcemia, hypercalciuria or nephrolithiasis, and hyperuricemia. On the opposite, PTH1R agonists may have an advantage over ROMO in low-bone turnover states and in cases of rare complications associated with prolonged bone turnover suppression, such as the osteonecrosis of the jaw and the atypical fractures. ROMO is contraindicated in patients with a history of myocardial infraction or stroke and should be used with caution in patients with cardiovascular risk factors. Among osteoanabolic agents only TPTD is approved for the treatment of male osteoporosis and glucocorticoid-induced osteoporosis. Finally, convenience of administration, reimbursement by national health systems and length of clinical experience may influence the decision of which osteoanabolic agent to use.