Glucocorticoid- induced bone loss is the most common cause of drug-related osteoporosis. It is especially severe in patients over 50 years of age and in those women who are postmenopausal. The important anti-inflammatory and immunosuppressive properties of this class of drugs have prompted their extensive use; however, side effects are many and bone loss resulting in vertebral fractures is the most incapacitating. Glucocorticoid excess produces bone loss by two primary mechanisms: (1) suppression of osteoblast function and (2) inhibition of intestinal calcium absorption leading to secondary hyperparathyroidism and increased bone resorption by osteoclasts. Attempts to treat glucocorticoid- induced osteoporosis include calcium, vitamin D3 replacement and anti-resorptive agents that include bisphosphonates, calcitonin and estrogen. All of these therapies seem to slow further bone loss but none have been able to increase bone mass. Recently, studies in vivo in humans and animals have shown that parathyroid hormone (PTH) administered intermittently in relatively low doses stimulates bone formation. This is in contrast to its well established ability to stimulate bone resorption when it is given in high doses continuously. The mechanisms of these paradoxical effects of PTH on bone are poorly understood, but recent studies in vitro suggest that the anabolic effects may be related to the ability of PTH to stimulate osteoblasts to produce insulin-like growth factor (IGF-I). The purpose of the proposed investigation is to determine if treatment with synthetic human parathyroid hormone fragment, 1-34, (hPTH1-34) will reverse glucocorticoid-induced osteoporosis in patients with rheumatic disease on chronic low dose glucocorticoid treatment. The osseous effects of PTH 1-34 will be monitored with conventional dual energy x- ray absorptiometry measurements of the spine, hip and forearm (mid- radius), quantitative computed tomography of the lumbar spine, and other outcome measurements which will include serial measurements of bone biochemical markers (including serum alkaline phosphatase, osteocalcin, urine calcium, and pyridinoline cross- links).
|Balooch, Guive; Yao, Wei; Ager, Joel W et al. (2007) The aminobisphosphonate risedronate preserves localized mineral and material properties of bone in the presence of glucocorticoids. Arthritis Rheum 56:3726-37|
|Lane, Nancy E; Yao, Wei; Balooch, Mehdi et al. (2006) Glucocorticoid-treated mice have localized changes in trabecular bone material properties and osteocyte lacunar size that are not observed in placebo-treated or estrogen-deficient mice. J Bone Miner Res 21:466-76|
|Hurley, Marja; Yao, Wei; Lane, Nancy E (2005) Changes in serum fibroblast growth factor 2 in patients with glucocorticoid-induced osteoporosis treated with human parathyroid hormone (1-34). Osteoporos Int 16:2080-4|
|Buxton, Eric C; Yao, Wei; Lane, Nancy E (2004) Changes in serum receptor activator of nuclear factor-kappaB ligand, osteoprotegerin, and interleukin-6 levels in patients with glucocorticoid-induced osteoporosis treated with human parathyroid hormone (1-34). J Clin Endocrinol Metab 89:3332-6|
|Thompson, J M; Modin, G W; Arnaud, C D et al. (1997) Not all postmenopausal women on chronic steroid and estrogen treatment are osteoporotic: predictors of bone mineral density. Calcif Tissue Int 61:377-81|