Osteoporosis studies

Higher intakes of fruits, specifically superfruits and certain vegetables, are also associated with improved bone mineral density and reduced bone loss in both men and women. Clinical trial results indicate that a diet rich in fruits and vegetables preserves bone health. Other studies link bone health to superfruit phytochemicals such as carotenoids, flavonoids, quercetin, and vitamin C. For example, in the Framingham Osteoporosis Study conducted over four years at Tufts University, in Boston, loss of bone mineral density in hundreds of elderly women and men was inversely related to intake of dietary carotenoids—a phytochemical found in superfruits ... 

Tucker, K.L., K. Morita, N. Qiao, M.T. Hannan, L.A. Cupples, and D.P. Kiel. Colas, But Not Other Carbonated Beverages, Are Associated with Low Bone Mineral Density in Older Women The Framingham Osteoporosis Study. American Journal of Clinical Nutrition 84, no. 4 (October 2006) 936—42. 

Liu YJ, Zhang L, Pei Y et al (2013) On genome-wide association studies and their meta-analyses lessons learned from osteoporosis studies. J Clin Endocrinol Metab 98 E1278-E1282... 

Genant HK, Lucas J, Weiss S, et al. Low-dose esterified estrogen therapy Effects on bone, plasma estradiol concentrations, endometrium, and lipid concentrations. Estratab/Osteoporosis Study Group. Arch Intern Med 1997 157 2609-2615. 

Hannan MT, Felson DT, Dawson-Hughes B, et al. Risk factors for longitudinal bone loss in elderly men and women The Framingham Osteoporosis Study. J Bone Miner Res 2000 15 710-720. 

Genant, H. K., Lucas, J., Weiss, S., Akin, M., Emkey, R., McNaney-Flint, H., Downs, R., Mortola, J., Watts, N., and Yang, H. M. (1997). Low-dose esterified estrogen therapy Effects on bone, plasma estradiol concentrations, endometrium, and lipid levels. Estra-tab/Osteoporosis Study Group. Arch. Intern. Med. 157, 2609-2615. 

Hormone replacement therapy has a checkered history. At one time, the medical community was convinced that it reduced a woman s risk of heart disease after menopause, but the accumulated data don t bear this out. While there is evidence that the therapy increases bone strength and reduces the risk of osteoporosis, studies have also shown a link with breast cancer. These days, a significant number of women are looking instead to natural therapies, which they perceive to be safer. 

The manufacturer notes that in phase IH osteoporosis studies of risedronate, no clinically relevant interaetions were noted, even though aspirin and NSAIDs being used by 33% and 45% of patients, respectively. Similarly, in a retrospective analysis of a 2-year placebo-controlled study, in those using regular NSAIDs (about two-thirds of patients) there was no difference in incidence of upper gastrointestinal adverse events between those given risedronate and those given placebo. ... 

Incidence of vertebral fi acture in europe results from the European Prospective Osteoporosis Study (EPOS). Journal of Bone and Mineral Research, 2002, 17, 716-724. 

Ascorbic acid also forms soluble chelate complexes with iron (142—145). It seems ascorbic acid has no effect on high iron levels found in people with iron overload (146). It is well known, in fact, that ascorbic acid in the presence of iron can exhibit either prooxidant or antioxidant effects, depending on the concentration used (147). The combination of citric acid and ascorbic acid may enhance the iron load in aging populations. Iron overload may be the most important common etiologic factor in the development of heart disease, cancer, diabetes, osteoporosis, arthritis, and possibly other disorders. The synergistic combination of citric acid and ascorbic acid needs further study, particularly because the iron overload produced may be correctable (147). 

In the treatment of diseases where the metaboUtes are not being deUvered to the system, synthetic metaboUtes or active analogues have been successfully adrninistered. Vitamin metaboUtes have been successfully used for treatment of milk fever ia catde, turkey leg weakness, plaque psoriasis, and osteoporosis and renal osteodystrophy ia humans. Many of these clinical studies are outlined ia References 6, 16, 40, 51, and 141. The vitamin D receptor complex is a member of the gene superfamily of transcriptional activators, and 1,25 dihydroxy vitamin D is thus supportive of selective cell differentiation. In addition to mineral homeostasis mediated ia the iatestiae, kidney, and bone, the metaboUte acts on the immune system, P-ceUs of the pancreas (iasulin secretion), cerebellum, and hypothalamus. 

Furthermore, peptidomimetic SH2 domain inhibitors for Src, such as AP-22408 have been designed that interfere with effector binding and thereby disrupt signal transduction. AP-22408 decreases bone resorption in animal studies and may be a promising drug to treat osteoporosis and other bone diseases, such as Paget s disease and osteolytic bone metastasis. 

Several other inhibitors of nonreceptor PTKs are currently in development but only a few of them are studied in clinical trials. Noteworthy, Dasatinib does not only inhibit c-Abl, but also potently blocks Src activity, a property that may contribute to its beneficial clinical effects in CML. Other kinase inhibitors being developed that inhibit c-Abl and/or Src are AZD-0530, AP-23994, PD-0183805, SU-6656, and Bosutinib (SKI-606). Furthermore, peptidomimetic SH2 domain inhibitors for Src, such as AP-22408 have been designed that decrease bone resorption and may be promising drugs to treat osteoporosis and other bone diseases, such as Paget s disease and osteolytic bone metastasis. 

Studies have demonstrated that treatment with soy or phytoestrogen enriched diets is effective in conserving bone in rodent models of osteoporosis (Anderson and Gamer, 1998 Ishimi et al, 2000 Draper et al, 1997). The mechanism of action of phytoestrogens on bone health is unclear but several mechanisms including inhibition of bone resorption and stimulation of bone formation maybe involved (Fanti etal, 1998 Ishimi e/a/., 1999 Picherit eta/., 2000). Limited data from studies in postmenopausal women have indicated that phytoestrogen supplements have a small, beneficial effect on bone loss in the lumbar spine (Alekel et al, 2000 Potter et al, 1998 Somekawa et al, 2001). 

PRINCE R L, SMITH M, DICK I M, PRICE R I, WEBB P G, HENDERSON N K and HARRIS M M (1991) Prevention of postmenopausal osteoporosis. A comparative study of exercise, calciiun supplementation, and hormone-replacement therapy. N Eng J Med 325, 1189-95. 

It has been shown that in postmenopausal women habitually high intakes of dietary isoflavones are associated with higher bone mineral density (BMD) values at both the spine and hip region (Mei et al, 2001). It is conceivable that an isoflavone-rich diet may help to reverse the state of secondary hyperparathyroidism associated with estrogen withdrawal and hence lower the rate of bone turnover in postmenopausal women, thus reducing the risk of osteoporosis (Valtuena et al, 2003). Phytoestrogens could be used as natural SERMs (Brzezinski and Debi, 1999) and some studies (Setchell, 2001 and refs therein) support such an idea since the molecular targets of... 

One chronic adverse effect that is of concern is osteoporosis.32,33 Carbamazepine, phenytoin, phenobarbital, oxcarbazepine, and valproate have all been shown to decrease bone mineral density, even after only 6 months of treatment. Data on the relationship between other AEDs and osteoporosis are not currently available. Multiple studies have shown the risk of osteoporosis due to chronic AED use to be similar to the risk with chronic use of corticosteroids. Patients taking carbamazepine, phenytoin, phenobarbital, or valproate for longer than 6 months should take supplemental calcium and vitamin D. Additionally routine monitoring for osteoporosis should be performed every 2 years, and patients should be instructed on ways to protect themselves from fractures. 

Thiazide diuretics decrease urinary calcium excretion and may decrease bone turnover. However, their effects on bone mineral density and fracture rates have not been studied in controlled trials. Thiazide diuretics are not recommended solely for potential beneficial effects in osteoporosis. 

Interest in the role of HMG-CoA reductase inhibitors (statins) in the treatment of osteoporosis came from boneforming properties seen in animal studies. However, controlled clinical trials are needed. 

Compared with postmenopausal osteoporosis, few clinical trials have been conducted evaluating therapies in men. Although alendronate and calcitonin have both been studied, only alendronate reduces fracture rates in men. Teriparatide also has been studied, but no data are available yet on fracture rates. At this time, alendronate and teriparatide are approved by the FDA for the treatment of osteoporosis in men. Owing to proven benefit in reducing fractures and relative safety, alendronate should be considered first-line treatment for primary osteoporosis in men. Teriparatide should be reserved as alternate therapy in this population. 

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