New bone formation

The bisphosphonates inhibit osteoclastic resorption of bone by binding to the hydroxyapatite crystals of bone. When osteoclasts first attach to bone in the active resorp-tive sites, the bisphosphonates are released from that bone. The release of these compounds locally prevents further osteoclastic attachment to those resorptive surfaces. The bisphosphonates also may inhibit resorption by inducing apoptosis of osteoclasts and by inhibiting release of interleukins and other compounds involved in bone resorption. The net result of actions of these compounds is inhibition of bone osteoclastic resorption. This action allows new bone formation to catch up in the remodeling process and can result in a net gain in bone density. 

These individuals have areas of increased bone resorption and other areas of abnormal new bone formation. The abnormal bone formation can result in pain, deformity, and fracture of affected bones. The bisphospho-nates and calcitonin are most commonly used in the treatment of this disease. Long-term continuous use of bisphosphonates can be associated with the induction of osteomalacia through a direct impairment of new bone formation. Therefore, the bisphosphonates are given in a cyclic pattern to treat Paget s disease. 

A. Paget s disease is often asymptomatic and picked up on plain bone films. Patients with Paget s disease should have their serum calcium level determined to make sure that they are not hypercalcemic from excessive bone resorption, their serum alkaline phosphatase measured as a marker of new bone formation, a bone scan to determine whether other bones are involved, and a 24-hour urinary hy-droxyproUne measurement to assess bone resorption. The patient who has minimal involvement and is biochemically normal does not need pharmacological therapy. No studies indicate that early treatment slows progression in individuals with the more severe form of this disorder. 

Mechanism of Action A synthetic polypeptide hormone that acts on bone to mobilize calcium also acts on kidney to reduce calcium clearance, increase phosphate excretion. Therapeutic Effect Promotes an increased rate of release of calcium from bone into blood, stimulates new bone formation. 

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. 

Teriparatide, the recombinant form of PTH 1-34, is approved for treatment of osteoporosis. Teriparatide is given in a dosage of 20 meg subcutaneously daily. Like fluoride, teriparatide stimulates new bone formation, but unlike fluoride, this new bone appears structurally normal and is associated with a substantial reduction in the incidence of fractures. Teriparatide is approved for use for only 2 years. Trials examining the sequential use of teriparatide followed by a bisphosphonate after 1 or 2 years are in progress and look promising. Giving teriparatide with a bisphosphonate has not shown greater efficacy than the bisphosphonate alone. 

The combined use of estradiol and dydrogesterone reduce both diastolic and systolic blood pressures in postmenopausal women in whom the diastolic pressure had been raised (3). Evidence is also advanced from various quarters that adding a progestogen to adequate dosages of an estrogen promotes new bone formation, restores bone that has been lost and reduces the risk of carcinoma of the breast. 

Fluoride Stimulates new bone formation prevents formation of dental cavities Men 4 mg/d Women 3 mg/d... 

Radium, similarly to calcium, deposits in bone within those areas where new bone mineral is being formed and also on all bone surfaces. Radium remains in those areas of new bone formation, but the radium deposits on bone surfaces eventually move into the depths of compact bone as new bone matrix is deposited on top of them. In this deposition process, short-lived radium-224 rapidly decays, leaving no radioactivity within bone whereas, long-lived radium-226 remains in the skeleton indefinitely (Rowland 1966). Mays et al. (1975) have demonstrated that the radon to radium ratio in bone increased with time after injection in beagles. 

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 and PTH promote new bone formation and can increase bone mineral density in subjects who... 

The inorganic component of bone is primarily platelike (20 to 80 nm long and 2 to 5 nm thick) crystalhne hydroxyapatite, Ca5(P04)3(0H) or HA (Kaplan et al., 1994 Park and Lakes, 1992). Small amounts of impurities may be present in the mineralized HA matrix for example, carbonate may replace phosphate groups, whereas chloride and fluoride may replace hydroxyl groups. Because release of ions from the mineral bone matrix controls cell-mediated functions, the presence of impurities may impact important biological aspects (and, subsequently, affect chemical and mechanical properties of bone) that are critical to normal bone function for example, impurities present in the mineralized matrix may affect cellular function(s) that influence new bone formation (Kaplan et al., 1994 Park and Lakes, 1992). 

HRT has been shown to be effective in reducing bone loss and fractures in postmenopausal women. It inhibits bone resorption and stimulates new bone formation [5]. When HRT is given in the first five to ten years of menopause the long-term risk of osteoporotic fractures is halved [5]. 

Begovac J, Bayer K, Krpan D, Kusec V. Osteosclerosis and periostal new bone formation during indinavir therapy. AIDS 2002 16(5) 803-4. 

E The addition of testosterone to HRT regimens can promote new bone formation, improve libido and sex drive, and improve moodiness, anxiety, and irritability (psychological symptoms). Negative effects, however, can include hirsutism, virilization, an increase in acne, and a reduction in HDL-C. 

The growth plate chondrocytes undergo proliferation, growth, degradation, mineralization, and resorption and provide the support structure for new bone formation. Bones can increase in length and width through this process. Endochondral ossification occurs near the base of the articular cartilage at the joints. 

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