Sequential Parathyroid Hormone/Alendronate Therapy for Osteoporosis—Robbing Peter to Pay Paul?

This is the authors' abstract. We don't add key points for this paper.

Although we currently have multiple Food and Drug Administration-approved antiresorptive therapies for the treatment of postmenopausal osteoporosis, the gains in vertebral bone mass approach only 6–7% over 3 yr with single-agent antiresorptive therapy (1–3) and up to 8–9% over 3 yr with two antiresorptive agents given simultaneously (4). Because bone mass has often decreased an average of 30% when postmenopausal women experience fractures and greater increases in bone mass are associated with greater vertebral fracture reduction (5), investigators have, therefore, searched for an ideal agent(s) to increase bone formation while suppressing or maintaining the rate of bone resorption. Previous studies have shown that PTH stimulates both bone formation and resorption with a greater net impact on bone formation, resulting in an increase in bone mass, particularly in trabecular bone (6). However, the “presentation” of PTH is crucial. When PTH is given as a constant infusion to animals or in disease states such as hyperparathyroidism where the levels are constantly elevated, the result is a loss of bone, especially at cortical sites (6–8). In contrast, like many other endocrine systems, when the hormone is presented in a pulsatile or intermittent fashion, it stimulates a net increase in bone mass at mainly trabecular sites. However, one concern with the anabolic agent PTH, when given as an intermittent injection, has been the potential trade-off of “robbing Peter to pay Paul.” Several studies involving PTH treatment have shown either a maintenance or loss of cortical bone at some sites in comparison with improvements in vertebral bone mass, or trabecular bone (9–12), which may be related to an increase in the remodeling space (6). This is a critical issue because if bone mass is only maintained, potentially lost, or placed in a more fragile and biomechanically insecure state at clinically relevant cortical sites, hip fractures may not be reduced—a much more costly and morbid event than vertebral fractures. However, lack of vitamin D sufficiency in patients at baseline or differences between PTH(1-34) and PTH(1-84) absorption, carriers, and circulating time may contribute to observed differences in cortical bone. A second concern is that, following discontinuation of anabolic therapy with PTH, patients may then lose bone and return to their previous baseline after withdrawal of therapy (9).