Osteoporosis Pathogenesis

Mcllwain HH. Glucocorticoid-induced osteoporosis Pathogenesis, diagnosis, and management. Prev Med 2003 36 243-249. 

Lukert bp and Raisz LG (1990) Glucocorticoid-induced osteoporosis pathogenesis and management. Ann Intern Med 112 352-364. 

MANOLAGAS s c (2000) Birth and death of bone cells basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis. Endocr Rev. 21 (2) 115-37. 

Osteoporosis associated with RA follows a multifaceted pathogenesis, but the primary mechanism likely is mediated by osteoclast activity.12 The cytokines involved in the inflammatory process directly stimulate osteoclast and inhibit osteoblast activity. Additionally, arthritis medications can lead to increased bone loss. Bone mineral density should be evaluated at baseline and routinely using dual-energy x-ray absorptiometry.11,12... 

There have been reviews of the mechanisms and adverse effects of glucocorticoids in rheumatoid arthritis (205) and the pathogenesis, diagnosis, and treatment of glucocorticoid-induced osteoporosis in patients with pulmonary diseases (206). Several mechanisms underlie the effect of glucocorticoids on bone, both biochemical and cellular. Effects on calcium are ... 

Cysteine proteases play key roles in the pathogenesis of a variety of disease states including osteoporosis [49], muscular dystrophy [50] and several CNS-related disorders [51]. A 100-member library of a-ketoamides 50 was generated via a two-step one-pot synthesis, in which the initial condensation was followed by a pyridinium dichromate (PDC) oxidation (Scheme 11.9). Yields were respectable, ranging from 53 to 75%. Note that a-ketoamides are potential reversible inhibitors with the ability to form hemi-thioacetals with the active thiol of cysteine residues. 

Rao et al. (2003) concluded that lycopene inhibited basal and PTH-stimulated osteoclastic mineral resorption and formation of TRAP+ multinucleated osteoclasts, as well as the ROS produced by osteoclasts. These findings are new and may be important in the pathogenesis, treatment, and prevention of osteoporosis. 

Markers of bone remodeling were very useful when used in clinical studies that were intended to learn and understand the pathogenesis of osteoporosis, and the... 

Cholestasis-linked osteopathy (M. Loeper et al., 1939), which occurs much more frequently in the form of osteoporosis than osteomalacia, can be expected in up to 50% of cases. The pathogenesis is complex. Vitamin D status can be examined by determining 25-OH-cholecal-ciferol in the serum. Intestinal calcium loss and reduced calcium absorption due to vitamin D deficiency are key pathogenetic factors. It is still a matter of debate whether vitamin K deficiency (which can lead to reduced osteocalcin synthesis) and deficiencies in IGF I and II (which can cause dysfunction of the osteoblasts) are possible causes of this condition. Muscle and bone pain are frequent clinical symptoms, occurring mainly in the wrists and ankles. 

Raisz LG. Pathogenesis of osteoporosis concepts, conflicts, and prospects. J Clin invest 2005 115 3318-3325. 

R. S. Weinstein and S. C. Manolagas Bone cell apoptosis implications for the pathogenesis and treatment of osteoporosis. Physiology in Medicine 108, 153 (2000). 

Manolagas SC, Weinstein RS. New developments in the pathogenesis and treatment of steroid-induced osteoporosis. J Bone Miner Res 1999 14 1061-1066. 

Recently, Riggs et al. (1998) proposed a unitary model for involutional osteoporosis, in which estrogen deficiency plays a central role in the pathogenesis of the disease in both sexes. In addition, calcium malnutrition and calcium malabsorption as a consequence of hypovitaminosis D are considered to be of great significance in the development of osteoporosis (Barrett-Connor 1989, Bronner 1994, Heaney 2002). 

If PTH contributes to the pathogenesis of osteoporosis, PTH antagonists may be effective for its treatment. Until such agents are tested in osteoporotic patients, however, this use is quite speculative. 

In areas of osteoporosis, the calcified bone is progressively replaced by the softer components of the skeleton (fibrous tissue, fat, and marrow). The pathogenesis of osteoporosis has not been established and therefore an adequate classification is not available. Cases of osteoporosis are grouped in two main categories those patients in whom osteoporosis results from endocrine or vitamin imbalance, and the idiopathic cases of osteoporosis, which cannot be traced to a well-established pathogenesis [26-28]. 

Elucidation of thyrocalcitonin s mechanism of action hopefully may provide new clues on the pathogenesis of osteoporosis (lack of hormone) and such diseases as Albers-Sch5nberg disease (osteopetrosis marble disease). 

The role of calcitonin in the pathogenesis of these diseases remains to be proven. It has been suggested that osteopetrosis is caused by an increased secretion of calcitonin in contrast, osteoporosis could be caused by a defect in calcitonin. Certainly some medullary carcinomas of the thyroid are associated with elevated levels of calcitonin and these tumors are not usually associated with osteopetrosis. The regulation of calcium levels in blood by parathormone and calcitonin is summarized in Fig. 5-14. For further information on the relationship between calcium metabolism and bone disease, read the book of Rasmussen and Bordier [38]. 

Patients with Cushing s disease develop marked osteoporosis which affects the skull, the vertebrae, and other bones. The spotty loss of calcium in the flat bones of the skull leads to the appearance of the moth-eaten skull and the softening of the vertebrae may be so marked that the intervertebral disc burrows into the body of the vertebra. The pathogenesis of osteopor-esis in Cushing s disease is far from elucidated. Osteoporosis can result from decreased osteoblastic activity, increased osteoclastic activity, a negative calcium balance, or the elaboration of an abnormal matrix. 

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