Bone-forming Agents
Abstract
Peptides From the Parathyroid Hormone Family
Peptides from the parathyroid hormone (PTH) family have been investigated in the management of osteoporosis for over 30 years.1 A continuous endogenous production or exogenous administration of PTH, as is the case in primary or secondary hyperparathyroidism, can lead to deleterious consequences on the skeleton, particularly on cortical bone. However, intermittent administration of PTH (e.g. through daily subcutaneous injections) results in an increase in the number and activity of osteoblasts, leading to an increase in bone mass and an improvement in skeletal architecture in both the trabecular and cortical skeleton. This treatment also increases cortical bone width.
The full length (1–84) molecule and the 1–34 N-terminal fragment are currently used for the management of osteoporosis. Based on their respective molecular weights, the equivalent dose of 1–34 fragment, relative to the 1–84 molecule, is 40% (e.g. 20μg and 40μg of 1–34 PTH is equivalent to 50μg and 100μg of 1–84 PTH, respectively).
In order to assess the effects of the 1–34 N-terminal fragment of PTH on fractures, 1,637 post-menopausal women with prior spine fractures were randomly assigned to receive 20μg or 40μg of 1–34 PTH or placebo, subcutaneously self-administered daily. Spine radiographs were obtained at baseline and at the end of the study (median duration of observation, 21 months) and serial measurements of bone mass were performed by dual-energy X-ray absorptiometry (DXA).
New spine fractures occurred in 14% of the women in the placebo group and in 5% and 4% of the women in the 20- and 40-μg dose groups, respectively. The relative risk of fracture compared with the lacebo group was 0.35 and 0.31 (95% confidence interval (CI), 0.22–0.55 and 0.19–0.50), respectively. New non-spine fractures occurred in 6% of women in the placebo group and 3% of those in each PTH group (relative risk (RR), 0.47 and 0.46; 95% CI, 0.25–0.88 and 0.25–0.86, respectively). PTH had only minor side effects (occasional nausea and headache).2
The anti-fracture efficacy of PTH on spine fracture was not modulated by the age of the subjects (<65 years of age, 65–75 years of age or >75 years of age), prevalent spinal bone mineral density (BMD) values (Tscore <-2.5 or >-2.5) or number of prevalent fractures (one, two or more fractures).3
