Current Status of Bone-Forming Therapies for the Management of Osteoporosis.

In patients with osteoporosis and severely reduced bone mass and/or recurring fractures, antiresorptive therapy may not be the optimal first-line treatment. Two recent clinical trials comparing bone-forming treatment with antiresorptive therapy have demonstrated that bone-forming treatment is superior in reducing the fracture risk in patients with severe osteoporosis. All of the currently available bone-forming agents-teriparatide, abaloparatide, and romosozumab-increase bone mineral density (BMD) and reduce the fracture risk; however, the effect wears off with time and treatment is therefore only transient. Thus, a bone-forming therapy should be followed by antiresorptive treatment with a bisphosphonate or denosumab. The BMD response to bone-forming treatment is reduced in patients previously treated with antiresorptive drugs; however, based on the findings of the VERO trial, the anti-fracture efficacy of bone-forming treatment in comparison with antiresorptives seems to be preserved. This review provides an overview of the existing bone-forming therapies for osteoporosis including considerations of sequential and combination therapy.

The clinical potential of romosozumab for the prevention of fractures in postmenopausal women with osteoporosis.

The glycoprotein sclerostin inhibits activation of the canonical Wnt pathway and thereby suppresses bone formation by inhibiting the osteoblasts. Additionally, sclerostin increases bone resorption by stimulating the production of receptor activator of nuclear factor kappa-ß-ligand (RANKL). Romosozumab (ROMO) is a monoclonal antibody against sclerostin. Phase III clinical trials in postmenopausal women with osteoporosis have shown that ROMO increases bone mineral density at the lumbar spine and hip and reduces the risk of vertebral and clinical fractures in comparison with placebo. In women with severe osteoporosis, ROMO reduces the risk of vertebral, nonvertebral and clinical fractures in comparison with alendronate. ROMO is the first treatment for osteoporosis with dual action, and may become a valuable tool for improving the treatment of osteoporosis. At present, the approval of ROMO by the authorities is awaiting further investigations of a potential increased risk of cardiovascular events associated with ROMO treatment.

Non-parathyroid hypercalcemia associated with paraffin oil injection in 12 younger male bodybuilders: a case series.

INTRODUCTION: Injection of paraffin oil to augment muscles size is a troubling phenomenon known to cause a foreign body reaction with formation of granulomas. In a few case reports, long-term side effects have been reported in terms of hypercalcemia and renal failure. METHODS: We identified a case series of 12 male bodybuilders presenting with non-parathyroid hypercalcemia who previously had injected paraffin oil to increase muscles size. RESULTS: At admission, all patients had moderate-to-severe hypercalcemia with suppressed PTH levels and impaired renal function. Calcitriol levels were within the normal range or slightly elevated. Follow-up measurements showed marked hypercalciuria with nearly normal levels of bone turnover markers. A correlation was found between levels of peptidyl dipeptidase and calcitriol (R = 0.812, P = 0.050). Treatment with antiresorptive agents seemed less effective than glucocorticoids, which resulted in a significantly lowering of ionized calcium levels and improved renal function, although no patients were cured by this treatment. Immunosuppression with azathioprine or mycophenolate may have a glucocorticoid-saving effect. One patient had surgery with removal of affected muscle tissue, without any apparent effect on plasma calcium levels. CONCLUSION: The hypercalcemia and associated hypercalciuria seems to be due to an intestinal hyperabsorption of calcium. It remains to be elucidated, whether an increased calcitriol synthesis within granulomas is the only (main) mechanism by which intestinal calcium absorption is increased. Glucocorticoids seem most appropriate as the first choice for treatment. Bodybuilders should be warned against use of intramuscular oil injections (and other substances), as this may have severe adverse health consequences.