Influence of Dosing Interval and Administration on the Bone Metabolism, Skeletal Effects, and Clinical Efficacy of Parathyroid Hormone in Treating Osteoporosis: A Narrative Review

Recombinant human parathyroid hormone (PTH) is the key anabolic agent used for preventing fracture in postmenopausal women with osteoporosis. In bone metabolism, PTH signaling is mediated through a G protein–coupled receptor that affects various post-receptor signaling pathways. Results of preclinical and clinical studies have shown that PTH improves both the structure and strength of bone tissue. Once daily subcutaneous injection of the PTH fragment, teriparatide (PTH [1-34]), is the most commonly recommended formulation and dosing strategy in clinical practice. However, other dosing intervals, formulations, and routes have been investigated in preclinical and clinical studies. In particular, once-weekly and cyclical administration have been investigated mainly as a means of reducing the high direct costs of treatment. In preclinical studies, bone formation/resorption markers, bone mineral density measurements, and histomorphometric parameters improved with both once-daily and once-weekly administration. However, the magnitude and duration of such improvements were generally greater with once-daily PTH administration. In clinical studies, reductions in fracture incidence were also noted with both once-daily and once-weekly PTH administration, although improvements in nonvertebral fractures are less evident with once-weekly administration. This narrative review details the differences between PTH formulation and dosing strategies in relation to preclinical and clinical efficacy/safety parameters, although it should be stressed that no head-to-head studies allow direct comparisons. This review also seeks to outline practical considerations involved with PTH prescribing and new directions in research regarding routes of administration.