Antiresorptive agent

Of the antiresorptive agents available, bisphosphonates provide the greatest BMD increases and fracture risk reductions. Fracture reductions are demonstrated as early as 6 months, with the greatest fracture reduction seen in patients with lower initial BMD and in those with the greatest BMD changes with therapy. 

Discontinuation of therapy results in a decrease in BMD, but some antifracture efficacy appears to be maintained. Sequential therapy with teriparatide followed by an antiresorptive agent (e.g., bisphosphonate) should be considered to maintain BMD gains. 

The most extensively used animal model to evaluate the action of SERMs on bone has been the ovariectomized (OVX) rat. In rats, tamoxifen antagonizes bone resorption and uterine growth (Turner et al. 1987,1988) and reduces the number and size of osteoclasts. The inhibitory effect on bone resorption of tamoxifen has also been reported in dogs and immobilized male rats (Wakley et al. 1988 Waters et al. 1991). As an antiresorptive agent, however, tamoxifen is less effective than 17/3-estradiol (17/9E2) (Williams et al. 1991) and has no effect when the endogenous production of estrogens is normal (Evans et al. 1994). 

Wasnich, R. D., and Miller, P. D. (2000). Antifracture efficacy of antiresorptive agents are related to changes in bone mineral density. /. Clin. Endocrinol. 85,231-236. 

Typical changes in bone mineral density with time after the onset of menopause, with and without treatment. In the untreated condition, bone is lost during aging in both men and women. Fluoride, strontium (Sr2+), and parathyroid hormone (PTH) promote new bone formation and can increase bone mineral density in subjects who respond to it throughout the period of treatment, although PTH also activates bone resorption. In contrast, estrogen, calcitonin, and bisphosphonates block bone resorption. This leads to a transient increase in bone mineral density because bone formation is not initially decreased. However, with time, both bone formation and bone resorption are decreased with these pure antiresorptive agents, and bone mineral density reaches a new plateau. 

Combining parathyroid hormone with antiresorptive agents may prevent or minimize hypercalcemia. None of... 

Combining parathyroid hormone with antiresorptive agents may prevent or minimize hypercalcemia. None of 27 women randomized to estrogen plus parathyroid hormone PTHi 34 25 micrograms/day became hypercal-cemic during a 3-year study (13). 

Vitamin K is required for y-carboxylation of osteocalcin before incorporation into bone matrix. Low-vitamin-K diets are associated with high amounts of uncarboxylated osteocalcin, lower BMD, and higher hip fracture rates. Early research suggests added vitamin K, especially when combined with other antiresorptive agents, has a positive effect on bone health. Currently, however, supplements are not recommended. Although warfarin decreases clotting factor production by antagonizing vitamin K, it alone probably does not cause bone loss. 

Strontium ranelate is an orally active agent that can be classified as both an antiresorptive agent and a bone-forming agent (42,43). It is able not only to stimulate replication of preosteoblastic cells to promote bone formation but also is able to decrease osteoclastic activity to prevent bone resorption. Biochemical markers for bone formation (e g., bone-specific alkaline phosphatase), which normally decrease in the presence of antiresorptive therapy, are elevated in the presence of strontium ranelate (44). Lumbar spine BMD increased 11.4% in patients treated with this new agent. 

Farina C, Gagliardi S. Selective inhibitors of the osteoclast vacuolar proton ATPase as novel bone antiresorptive agents. Drug Discov. Today 1999 4(4) 163-172. 

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