Parathyroid Hormone, Calcitonin, Vitamin D: Adverse Effects

ADVERSE EFFECTS

With the exception of the possible development of a hypervitaminosis associated with high-dose administra-tion of vitamin D₂ or D₃,. Allergic reactions to the injection of calcitonin and PTH have occurred and chronic use of some bisphosphonates has been associ-ated with the development of osteomalacia. The princi-pal side effects of intravenous bisphosphonates are mild and include low-grade fever and transient increases in serum creatinine and phosphate levels. Oral bisphos-phonates are poorly absorbed and can cause esophageal and gastric ulceration. They should be taken on an empty stomach; the individual must remain upright for 30 minutes after ingestion.

Human Parathyroid Hormone

Human rPTH (1-34) has been produced by recombinant technologies, is now approved, and will soon be available for the treatment of osteoporosis. It is given subcuta-neously, 25 g/day cyclically for 12 to 18 months, to in-crease bone density in individuals with a history of frac-tures, severe osteopenia, or osteoporosis. PTHrP (1-36) has also been synthesized and is in early clinical trials.

Calcitonin

Calcitonin (Miacalcin, Miacalcin Nasal Spray) is a syn-thetic 32–amino acid polypeptide that is identical to salmon calcitonin. Salmon calcitonin is more potent than human calcitonin because of its higher affinity for the human calcitonin receptor and its slower metabolic clearance. Administration is by subcutaneous or intra-muscular injection or by nasal spray. The absorption of the nasal form is slower than that of the parenteral routes.

Vitamin D Compounds

Vitamin D comes in many formulations, including mul-tivitamin preparations, fish liver oils with or without vi-tamin A, combinations with calcium salts, and vitamin D preparations alone. Most forms of vitamin D contain ei-ther cholecalciferol (D₃) or ergocalciferol (D₂).

Cholecalciferol is pure vitamin D₃ derived from the ultraviolet conversion of 7-dehydrocholesterol to chole-calciferol. Ergocalciferol (vitamin D₂) is a sterol derived from yeast and fungal ergosterol. Calcitriol [Rocaltrol, 1,25-(OH)₂D₃] is the metabolically active vitamin D₃ compound. Dihydrotachysterol is a synthetic compound that may act somewhat more quickly than either vita-min D₂ or D₃.

Bisphosphonates

Multiple bisphosphonates compounds are available for both oral and intravenous use. Some [alendronate (Fosamax) and etidronate (Didronel)] are used for os-teoporosis, others [etidronate, tirludronate (Skelid), risedronate (Actonel)] for Paget’s disease, and yet oth-ers [pamidronate (Aredia), zoledronic acid] for the hy-percalcemia of malignancy.