pamidronate + zoledronate

Pamidronate and zoledronate are nitrogen-containing intravenous bisphosphonates being evaluated by the Medical University Innsbruck for the treatment of Multicentric Osteolysis, Nodulosis and Arthropathy (MONA) spectrum disorder. MONA is an ultra-rare autosomal recessive skeletal dysplasia caused by loss-of-function mutations in the matrix metalloproteinase 2 (MMP2) gene, characterized by progressive osteolysis (particularly of the carpal and tarsal bones), subcutaneous nodules, and arthropathy. These small molecule drugs function by binding to hydroxyapatite in bone and inhibiting farnesyl pyrophosphate synthase (FPPS) within osteoclasts. This inhibition disrupts the mevalonate pathway, preventing the prenylation of small GTP-binding proteins essential for osteoclast function and survival, thereby reducing bone resorption. Clinical observations from the Innsbruck study suggest that these bisphosphonates can significantly alleviate bone pain and improve bone mineral density in patients with MONA.

Brand names

ArediaZometaReclastAclasta

Other names

Bisphosphonates