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

Abstract

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. © 2017 The Authors. JBMR Plus is published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.

Once-Weekly Teriparatide Treatment Prevents Microdamage Accumulation in the Lumbar Vertebral Trabecular Bone of Ovariectomized Cynomolgus Monkeys

“…Although patients are routinely treated with daily teriparatide injections, a once-weekly treatment regime for teriparatide is already used in Japan [10] and South Korea [11] to treat osteoporotic patients with high fracture risk. Weekly teriparatide treatment can reduce the incidence of osteoporotic vertebral fractures by 78% in postmenopausal women with prevalent vertebral fractures [10].…”

Delayed and significant hypercalcaemia due to teriparatide therapy: a case report and review

“…Secondly, consideration should be given to changing to alternate day teriparatide [ 12 ] though definitive evidence on anti-fracture efficacy is lacking. However, a reduction in vertebral fractures has been identified in trials of once weekly teriparatide using 28.2 µg or higher doses [ 20 ]. Finally, therapy could be switched to abaloparatide which has a lower incidence of hypercalcaemia, though is not approved in Europe.…”

The role of intermittent PTH administration in conjunction with allogenic stem cell treatment to stimulate fracture healing

“…The literature still remains inconsistent regarding the best dosing concentration for bone formation in the fracture context. Rodent study dosing is typically 4 to 40 μg/kg per day, 30 while approved human dosing is 20 mg/day, which in rats is approximately equivalent to 0.3 to 0.5 μg/kg/day. 31 Nonetheless, the unclear receptor binding profile in rodents means the administered high dose may not be wholly absorbed or active, and therefore the acting dose may be much lower than the concentration administered.…”