Pathophysiology of growth hormone secretion disorders and their impact on bone microstructure as measured by trabecular bone score.

This article is focused on endocrine-mediated osteoporosis caused by growth hormone (GH) disorders; adult GH deficiency and acromegaly. GH and insulin like growth factor-1 (IGF-1) stimulate linear bone growth through complex hormonal interactions and activates epiphyseal prechondrocytes. GH, via receptor activator of nuclear factor-kappaB (RANK), its ligand (RANK-L), and the osteoprotegerin system, stimulates production of osteoprotegerin and its accumulation in bone matrix. Malfunction of this mechanism, could lead to specific bone impairment. However, the primary problem of bone disease in GH secretion disorders is the primary prevention of osteoporotic fractures, so it is important to determine bone quality that better reflects the patient's actual predisposition to fracture. A method estimating bone quality from lumbar spine dual X-ray absorptiometry (DXA) scans is trabecular bone score (TBS). TBS in addition to bone mineral density (BMD) is a promising predictor of the osteoporotic fracture risk in women with postmenopausal osteopenia. In acromegaly TBS better defines risk of fracture because BMD is normal or even increased. TBS helps to monitor the effect of growth hormone therapy. Despite these findings, TBS should not be used alone, but a comprehensive consideration of all fracture risk factors, BMD and bone turnover markers is necessary.

Stem cells in skeletal physiology and endocrine diseases of bone.

Self-renewing, multipotent progenitors of skeletal tissues are found within skeletal segments (skeletal stem cells) and coincide with adventitial reticular cells of bone marrow vessels in situ and with explanted clonogenic stromal cells ex vivo. These cells, which can be identified and prospectively isolated based on a minimal surface phenotype noted for expression of CD146, CD105 and alkaline phosphatase, are established during bone development through interactions with developing sinusoids. They represent a crucial crossroad of skeletal and hematopoietic physiology, as well as of endocrine regulation of bone growth and remodeling. In addition, they are central to major endocrine functions of bone itself, such as regulation of renal phosphate handling. Skeletal stem cells represent a central model system for investigating skeletal diseases, as tools for in vitro and in vivo models, for cell therapy-based strategies, or as targets for drugs.

Endocrine parameters of cystic fibrosis: back to basics.

Dramatic changes in the life expectancy of cystic fibrosis (CF) patients are occurring, creating a cohort of aging individuals experiencing long-term complications of this chronic disease. The two most common of these complications include CF-related diabetes and CF bone disease. The clinical implications of each have become better understood, as have potential therapies. However, data obtained from the basic science studies of both diseases have not been widely recognized. In this review, we focus on the known and hypothesized pathogenesis of these two disorders. Additionally, the molecular underpinnings of CF will be explained along with the potential interactions with endocrine disease phenotypes.

Vitamin D receptor activators can protect against vascular calcification.

An apparent conflict exists between observational studies that suggest that vitamin D receptor (VDR) activators provide a survival advantage for patients with ESRD and other studies that suggest that they cause vascular calcification. In an effort to explain this discrepancy, we studied the effects of the VDR activators calcitriol and paricalcitol on aortic calcification in a mouse model of chronic kidney disease (CKD)-stimulated atherosclerotic cardiovascular mineralization. At dosages sufficient to correct secondary hyperparathyroidism, calcitriol and paricalcitol were protective against aortic calcification, but higher dosages stimulated aortic calcification. At protective dosages, the VDR activators reduced osteoblastic gene expression in the aorta, which is normally increased in CKD, perhaps explaining this inhibition of aortic calcification. Interpreting the results obtained using this model, however, is complicated by the adynamic bone disorder; both calcitriol and paricalcitol stimulated osteoblast surfaces and rates of bone formation. Therefore, the skeletal actions of the VDR activators may have contributed to their protection against aortic calcification. We conclude that low, clinically relevant dosages of calcitriol and paricalcitol may protect against CKD-stimulated vascular calcification.