Menopause bisphosphonates

Osteoporosis Oral calcium supplementation (1000-5000 mg/day) Oral vitamin D Calcifediol (1000 lU/day) Calcitriol (0.5 mcg/day) Hormone-replacement therapy Calcitonin or oral bisphosphonates If daily intake less than 1000 mg elemental calcium Documented deficiency If kidney functioning If kidney not functioning Post-menopausal women without contraindications Documented loss in bone mineral density greater than 3% Data lacking for bisphosphonates in patients with Rl... 

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. 

Options for treatment include hormone replacement therapy (HRT), bisphosphonates, calcitriol, calcitonin, raloxifene, strontium ranelate, and teriparatide. Hormone replacement therapy is generally indicated for women who are under 50 years and are experiencing a premature menopause. Symptomatic menopausal women may opt to use HRT also, as the benefits outweigh the risks for up to 5 years treatment. They may choose an alternative treatment for osteoporosis if preferred. Hormone replacement therapy is not recommended for first line treatment for long-term prevention of osteoporosis in women over 50 years of age. 

Owing to the reduction in oestrogen levels during the menopause, an increase in bone loss is seen. However, HRT is generally not recommended as first-line therapy for the prophylaxis or treatment of postmenopausal osteoporosis. It should only be used where other therapies are contraindicated, not tolerated, or there is a lack of response. In chronic liver disease HRT may be used first line due to intolerance of other agents, for example bisphosphonates. 

Osteoporosis is of two forms- primary i.e. idiopathic and secondary. Primary osteoporosis is classified into type I and type II osteoporosis. Type I is referred to post menopausal osteoporosis which is the main type affecting women, characterized by rapid bone loss and affects women after the menopause, mainly in trabecular bone and is associated with vertebrae and distal radio fractures whereas type II also termed as senile osteoporosis occurs due to chronic deficiency of calcium, increase in parathormone activity and decrease in bone formation and is associated with aging. On the other hand secondary type results from inflammatory processes, endocrine changes, multiple myeloma, sedentariness and the use of drugs such as heparin, corticoid and alcohol [3]. Prevention is the main treatment of osteoporosis, for which bone mass peak and the prevention of postmenopausal reabsorption are critical elements. The common treatment of osteoporosis includes calcium consumption as calcium salts, vitamin D supplements, and hormone reposition [4], the use of calcitonin to modulate serum levels of calcium and phosphorous [5], the use of bisphosphonate, mainly alendronates [6], use of ipriflavone and sodium fluoride [7], besides physical activity to strengthen muscles, stimulate osteoblasts formation and prevent reabsorption. 

Bones are constantly dissolved by osteoclasts and remineralized by osteoblasts in response to mechanical forces. Osteoclasts possess an acidic compartment and pass demineralized bone products to the periosteum (Sect. 1). They develop in stress-induced bony microcracks and are activated by differentiation factors secreted by osteoblasts, especially after menopause. Menopausal osteoporosis is controlled by drugs that are a stable form of pyrophosphate (bisphosphonate) or cathepsin K inhibitors (Sect. 2). The calcium ion concentration of blood is raised by parathyroid hormone and a vitamin D derivative called calcitriol. Parathyroid hormone causes kidneys to excrete phosphate, retain calcium, and activate calcitriol production (Sect. 3). Calcitriol induces calcium transporter proteins in osteoclasts and intestinal epithelium, where they move calcium from bone or diet into blood (Sect. 4). The chapter concludes with a discussion of calcitonin which lowers blood calcium concentrations by reversing parathyroid hormone effects on the kidney and inhibiting osteoclast activity (Sect. 5). 

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