Parathyroid Hormone and Teriparatide for the Treatment of Osteoporosis: A Review of the Evidence and Suggested Guidelines for Its Use

Abstract

All therapies currently recommended for the management of osteoporosis act mainly to inhibit bone resorption and reduce bone remodeling. PTH and its analog, teriparatide [recombinant human PTH(1-34)], represent a new class of anabolic therapies for the treatment of severe osteoporosis, having the potential to improve skeletal microarchitecture. Significant reductions in both vertebral and appendicular fracture rates have been demonstrated in the phase III trial of teriparatide, involving elderly women with at least one prevalent vertebral fracture before the onset of therapy. However, there is as yet no evidence that the antifracture efficacy of PTH will be superior to the bisphosphonates, whereas cost-utility estimates suggest that teriparatide is significantly more expensive. Teriparatide should be considered as treatment for postmenopausal women and men with severe osteoporosis, as well as for patients with established glucocorticoid-induced osteoporosis who require long-term steroid treatment. Teriparatide should also be considered for the management of individuals at particularly high risk for fractures, including subjects who are younger than age 65 and who have particularly low bone mineral density measurements (T scores < or = 3.5). Teriparatide therapy is not recommended for more than 2 yr, based, in part, on the induction of osteosarcoma in a rat model of carcinogenicity. Total daily calcium intake from both supplements and dietary sources should be limited to 1500 mg together with adequate vitamin D intake (< or =1000 U/d). Monitoring of serum calcium may be safely limited to measurement after 1 month of treatment; mild hypercalcemia may be treated by withdrawing dietary calcium supplements, reducing the dosing frequency of PTH, or both. At present, concurrent therapy with antiresorptive therapy, particularly bisphosphonates, should be avoided, although sequential therapy with such agents may consolidate the beneficial effects upon the skeleton after PTH is discontinued.

Safety of osteoanabolic therapy: A decade of experience

“…(20,26,29,31) However, because many tissues and solid tumors could express the PTH/PTHrP receptor, it has been suggested that patients with a history of cancers in the past 5 years avoid PTH therapy. (75) There may be wisdom in this recommendation for those whose malignancies harbor osteoblastic potential, such as breast and prostate cancer. However, there is no information about changes in tumor behavior in response to PTH.…”

Molecular and cellular mechanisms of the anabolic effect of intermittent PTH

“…Daily injections of parathyroid hormone (PTH) amino-terminal peptide 1-34, or the full length protein PTH , increase bone mass and reduce the incidence of fracture in postmenopausal women, in elderly men, and in women with glucocorticoid-induced osteoporosis (reviewed in [1]). The anabolic effect of intermittent PTH has also been extensively demonstrated in mice and rats [2].…”

“…Accretion of bone mass in humans is most rapid during the first 6 to 12 months of PTH administration, and the response tends to wane thereafter [1]. Increased bone formation is manifested as early as 28 days as evidenced by a rise in the level of circulating markers of osteoblast function, and an increase in tetracycline-labeled surface in transileal biopsies [7][8][9].…”

“…Increased bone formation is manifested as early as 28 days as evidenced by a rise in the level of circulating markers of osteoblast function, and an increase in tetracycline-labeled surface in transileal biopsies [7][8][9]. By 6 months, indices of bone resorption have also increased [1,9]. Thus, the increased bone formation occurs without increased bone resorption in the initial stages of the response, whereas anabolism occurs within the context of increased remodeling after approximately 6 months.…”

Parathyroid hormone mediates bone growth through the regulation of osteoblast proliferation and differentiation

“…In the second, the effect of intermittent PTH treatment on cell proliferation within the ossicles was measured using luciferase tagged BMSCs in conjunction with in vivo bioluminescent imaging (BLI). Recent clinical studies conducted to evaluate the benefits of using combination therapy for postmenopausal osteoporosis treatment revealed the surprising findings that bisphosphonates blunted expected additive effects when used concurrently with PTH [12][13][14]. Hence, in the third strategy, PTH and bisphosphonate treatment were combined to gain new insight of how these two agents affect the pool of bone forming cells that facilitate new bone development.…”