Method of increasing bone toughness and stiffness and reducing fractures

Abstract

The invention relates to a method for increasing the toughness and / or stiffness of bone and / or reducing the likelihood and / or severity of bone fracture by administering a parathyroid hormone. The method can be employed to increase toughness or stiffness of bone at a site of a potential or actual trauma, such as the hip or spine of a person at risk of or suffering from osteoporosis. The method of the invention can reduce the incidence of vertebral fracture, reduce the incidence of multiple vertebral fractures, reduce the severity of vertebral fracture, and / or reduce the incidence of non-vertebral fracture.

Description

TECHNICAL FIELD [0001] This invention relates to methods for increasing the toughness and / or stiffness of bone and / or reducing the likelihood and / or severity of bone fracture by administering a parathyroid hormone. More particularly, the invention relates a method for increasing toughness or stiffness of bone at a site of a potential or actual trauma, such as the hip or spine of a person at risk of or suffering from osteoporosis. More particularly, the invention relates to a method of reducing the incidence of vertebral fracture, reducing the incidence of multiple vertebral fractures, reducing the severity of vertebral fracture, and / or reducing the incidence of non-vertebral fracture. BACKGROUND OF THE INVENTION [0002] Existing agents such as estrogen, bisphosphonates, fluoride, or calcitonin can prevent bone loss and induce a 3-5% increase of bone mass by refilling the remodeling space, but net bone formation is not significantly stimulated. The retention of bone by inhibition of b...

AI Technical Summary

Benefits of technology

[0009] The present invention includes a method for increasing the toughness and / or stiffness of bone, preferably cortical bone, and / or reducing the incidence and / or severity of fracture by administering a parathyroid hormone. More particularly, the invention relates to a method for increasing toughness or stiffness of bone at a site of a potential or actual trauma. Increasing toughness and / or stiffness of bone can be manifested in numerous ways known to those of skill in the art, such as increasing bone mineral density, increasing bone mineral content, increasing work to failure, and the like. In one embodiment, the method of the invention reduces the incidence or severity of vertebral and / or non-vertebral fractures. The method of the invention can be used to decrease the risk of such fractures or for treating such fractures. In particular, the method of the invention can reduce the incidence of vertebral and / or non-vertebral fracture, reduce the severity of vertebral fracture, reduce the incidence of multiple vertebral fracture, improve bone quality, and the like.

[0010] The method can increase toughness or stiffness at a site of a potential trauma, such as a hip or spine of a person with osteoporosis, or at another site having abnormally low bone mass or poor bone structure. The method can also increase bone toughness or stiffness at a site of an actual trauma, such as a fracture, for example, in a hip or vertebra. A preferred subject for the method of the invention is a woman or man at risk for or having osteoporosis, preferably a postmenopausal to woman, and is independent of concurrent hormone replacement therapy (HRT), estrogen or equivalent therapy, or antiresorptive therapy. In one embodiment, the patient also receives supplements of calcium and / or vitamin D.

Problems solved by technology

The retention of bone by inhibition of bone turnover may not be sufficient protection against fracture risk for patients who already have significant bone loss.

It is commonly believed that PTH administration in humans and in relevant animal models has a negative effect on cortical bone.

One concern raised by such studies is that there would be a loss of total skeletal bone mass due to the loss of cortical bone.

Continued loss of cortical bone would increase the fracture risk.

The effects of PTH on cortical bone have been investigated in nonhuman animals with Haversian remodeling, such as dogs, ferrets, sheep and monkeys, but sample sizes are typically too small for reliable statistical analysis.

Published studies of rodents have shown increased cortical bone mass during administration of PTH but a loss of this benefit after withdrawal of PTH.

Furthermore, technological limitations in biomechanical testing on the relatively short bones of rodents give rise to artifacts of measurement when an agent, such as a PTH, alters bone geometry to thicken the bone.

Such artifacts make extrapolation of rat cortical bone responses to those of humans or other animals with osteonal remodeling unreliable.

Therefore, the existing data for animals, like humans, undergoing Haversian remodeling indicates that PTH may have an adverse impact on cortical bone, causing net loss of bone mass through depletion of cortical bone.

The opposing effects of estrogen and PTH on cortical bone turnover make it particularly difficult to observe effects of just PTH during combination therapy with these two agents.

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