Osteoporosis case study

Gastrointestinal complaints (eg, nausea, diarrhea, vomiting, flatulence) are the most common adverse effects but rarely require discontinuation of therapy. Other potential adverse effects include headache and asthenia. Tenofbvir-associated proximal renal tubulopathy causes excessive renal phosphate and calcium losses and 1-hydroxylation defects of vitamin D, and preclinical studies in several animal species have demonstrated bone toxicity (eg, osteomalacia). Monitoring of bone mineral density should be considered with long-term use in those with risk factors for or with known osteoporosis, as well as in children. Reduction of renal function over time, as well as cases of acute renal failure and Fanconi s syndrome, have been reported in patients receiving tenofovir alone or in combination with emtricitabine. For this reason, tenofovir should be used with caution in patients at risk for renal dysfunction. Tenofovir may compete with other drugs that are actively secreted by the kidneys, such as cidofovir, acyclovir, and ganciclovir. 

In an effort to improve the benefit-to-risk ratio of PTH in the context of the uncertain relevance of the findings in rodents, it was strongly recommended that participation in clinical studies be limited to adults with severe osteoporosis who have completed bone maturation. It was further advised that any case of osteosarcoma (or other bone tumor) be immediately reported and long-term follow-up be conducted for patients treated with PTH. Importantly, subjects in clinical trials of PTH and PTH analogues should be informed about the occurrence of osteosarcomas in rodents. 

Epilepsy and osteoporosis are very common and frequently overlap. Nevertheless, the prevalence of low bone density appears to be disproportionately higher in patients with epilepsy, and patients with epilepsy have an excessive risk of fractures. A meta-analysis of 94 cohort studies and 72 case-control studies has shown that anticonvulsant treatment is highly associated with fractures (relative risk over 2) (117). Other risk factors were low body weight, weight loss, physical inactivity, consumption of corticosteroids, primary hjrperparathjroidism, type 1 diabetes melhtus, anorexia nervosa, gastrectomy, pernicious anemia, and age over 70 years. 

The dose (CdU)-response rate of increased calci-uria (> 9.8 mmol/24h) suggested a 10% prevalence of hypercalciuria when CdU exceeded 1.9 pg Cd/ 24h [31]. Hypercalciuria should be considered an early adverse tubulotoxic effect, because it may exacerbate the development of osteoporosis, especially in the elderly. A prospective study from 1992-1995 (median follow-up of 6.6 years) in the above-mentioned Cadmibel subcohort from the rural area showed for a two-fold increase in urinary Cd a significant (p<0.02) decrease of 0.01 g/ cm2 jn forearm bone density in post-menopausal women. In addition, the relative risks associated with doubled urinary Cd were 1.73 (95% Cl 1.16-2.57 p=0.007) for fractures in women and 1.60 (0.94-2.72 p=0.08) for height loss in men. Cadmium excretion in the four districts near the smelters was 22.8% higher (p=0.001) than in the six other districts, with fractme rates of 16.0 and 10.3 cases per 1000 person-year, respectively, and a population-attributable risk of 35%... 

Nieves, J.W., J.A. Grisso, and J.L. Kelsey. 1992. A case-control study of hip fracture Evaluation of selected dietary variables and teenage physical activity. Osteoporosis Int. 2(3) 122-127. Noordzij, M., C. Uiterwaal, L.R. Arends, et al. 2005. Blood pressure response to chronic intake of coffee and caffeine A meta-anal-ysis of randomized controlled trials. J. Hyperten. 23(5) 921-928. Nordmark, A., S. Lundgren, S. Cnattingius, and A. Rane. 1999. Dietary caffeine as a probe agent for assessment of cytochrome P4501A2 activity in random urine samples. Br. J. Clin. Pharmacol. 47(4) 397-402. 

The successful establishment of nondestructive NAA as an analytical technique for the study of the elemental composition of biological materials promoted the evaluation of its feasibility for determining some elements in living subjects by in vivo NAA (Anderson et al. 1964). From this first demonstration, the technique rapidly evolved (Ellis 1990). Currently, it is possible to measure total-body H, N, O, Na, P, Cl, K, and Ca and to determine most of the same elements in parts of the body, such as a limb or an organ. In special cases, additional important elements such as I (in thyroid), Cd (in kidney), as well as Mn, Fe, and Cu have been reported. The results of the measurements are used in clinical studies of mineral metabolism, nutrition, body physiology, and alterations in composition from clinical or enviromnental causes and diseases such as osteoporosis. 

In a cross-sectional study of the relation between duration and dosage of valproate monotherapy (mean duration of treatment 11 years) and bone mineral density in 41 adults with epilepsy, there was osteopenia in 24% but no cases of osteoporosis [336 ]. The duration and dosage of valproate monotherapy did not correlate with either bone mineral density or biochemical parameters. 

Tumorigenidty Osteosarcoma is postulated as a potential adverse reaction to parathyroid hormone analogues, based on animal studies, and another case has been reported in a 67-year-old man who took teriparatide 20 micrograms/day subcutaneously for 2 months, 7 years after a course of radiotherapy for recurrent prostate cancer [65 ]. However, the osteosarcoma occurred within the field of previous radiotherapy and the time course suggested that the osteosarcoma may have been present before teriparatide administration. The authors noted that 430 000 patients have been treated with teriparatide for osteoporosis and that there have been only two reported cases of osteosarcoma, which is consistent with the expected population incidence of 4-5 per million. However, the effect of teriparatide on the growth of an undiagnosed osteosarcoma is unknown, and so teriparatide should be used with caution in patients who have had previous radiotherapy. 

Although nonhuman primates have been useful in studies on the role of nutrition in a number of human diseases with an adult onset, they have been of little value in the case of osteoporosis because of the protracted time over which studies on this disease must be conducted. The cost of providing the numbers of animals necessary for statistical validity with adequate housing and veterinary care and with experimental diets over a period of one to two decades is generally prohibitive. 

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