Osteoporosis treatment bone mineral density

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. 

All postmenopausal women with a personal history of osteoporotic fracture and/or low bone mineral density with risk factors for osteoporosis should receive treatment for osteoporosis. 

Although most fragility fractures in women occur after age 50, certain groups of premenopausal women are at high risk for osteoporosis. The NOF recommends measuring bone mineral density in premenopausal women with risk factors in addition to sex and race, in whom treatment would be considered.1 Premenopausal women at risk for osteoporosis should follow all nonpharmacologic recommendations for exercise and adequate calcium and vitamin D intake. Currently, no good data... 

Osteoporosis affects some 75 million people in Europe, Japan and the USA combined. The condition is characterized by progressive thinning of the bones, leading to bone fragility and increased risk of fracture. Treatment with Forsteo increases bone mineral density and generally entails daily s.c. injection for several months at dosage levels of 20 pg active/dose. 

The past 3 years have seen tremendous advances in both the design of Cat K inhibitors and in our understanding of the effect of Cat K inhibition on bone remodeling. The structural diversity of Cat K inhibitors has expanded considerably from simple peptidomimetics to non-peptidic derivatives and even non-covalent inhibitors. The potency, selectivity and pharmacokinetic properties of key compounds are very attractive and seem well-suited to further development. The disclosure of clinical validation of the effect of Cat K inhibition on bone mineral density, plus the provocative data suggesting a decoupling of bone resorption and bone formation provides a compelling framework for further development of Cat K inhibitors for the treatment of osteoporosis. 

Treatment of postmenopausal women with osteoporosis with raloxifene (60mg/day or 120mg/day for 36 months) was found to significantly increase bone mineral density in the spine and femoral neck and decrease the risk of vertebral fracture compared to the placebo treatment.Treatment with raloxifene increased the risk of venous thromboembolism compared to the placebo group and was also associated with a lower risk of breast cancer and did not cause breast pain or vaginal bleeding. 

Etidronate and the other bisphosphonates exert a variety of effects on bone mineral homeostasis. In particular, bisphosphonates are useful for the treatment of hypercalcemia associated with malignancy, for Paget s disease, and for osteoporosis (see Newer Therapies for Osteoporosis). Contrary to expectations, some of the newer bisphosphonates appear to increase bone mineral density well beyond the 2-year period predicted for a drug whose effects are limited to blocking bone resorption. The bisphosphonates exert a variety of other cellular effects, including inhibition of l,25(OH)2D... 

In older women with asthma, who have an increased risk of osteoporosis, there was no significant change in bone mineral density after 1 year of treatment... 

In postmenopausal osteoporosis treatment with calcitriol plus etidronate or calcitonin produced improvement in spinal bone mineral density, but a high rate of nephrotoxic adverse events (17). 

Osteoporosis, trabecular bone being most affected, has been regularly observed in both sexes with chronic gonadorelin agonist treatment (48), and the duration of therapy for prostate cancer is inversely related to bone mineral density (49,50). Intravenous pamidronate may prevent bone loss in these patients (51,52). 

Therapeutic efficacy in the treatment and prevention of bone loss in postmenopausal patients has been defined in terms of changes in bone mineral density (BMD) as well as fracture incidence. Although the occurrence of fracture is the clinical manifestation of osteoporosis, this disease is operationally defined by the WHO as a BMD equal or greater than 2.5 standard deviations below the young adult reference mean. In this regard, BMD has been shown to be an accurate predictor of some fractures, and it can be used as a diagnostic tool for at-risk individuals.4... 

Figure 20.8 illustrates the four basic drug effect patterns when the input or output parameter changes with an exponential time course. As an example of this type of disease progress model, consider postmenopausal osteoporosis reflected by the net loss of bone mass after the menopause. Bone loss may be due to decreased formation or increased resorption of bone. Figure 20.9 illustrates the time course of bone mass change due to increased bone loss and the effect of administering a drug to reduce that loss. For example, raloxifene has been shown to be beneficial in women with postmenopausal osteoporosis (11). The pattern of increase in bone mineral density observed after treatment with raloxifene or placebo resembles the curves shown in Figure 20.10. However, the treatment duration in this dataset was too short to identify the actual mechanism of raloxifene effect on disease progress.

Feldstein A, Elmer PJ, Orwoll E, et al. Bone mineral density measurement and treatment for osteoporosis in older individuals with fractures A gap in evidence-based practice guideline implementation. Arch Intern Med 2003 163 2165-2172. 

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