Bone formation, decrease

PTH is the most important regulator of bone remodelling and calcium homeostasis. PTH is an 84-amino acid polypeptide and is secreted by the parathyroid glands in response to reductions in blood levels of ionised calcium. The primary physiological effect of PTH is to increase serum calcium. To this aim, PTH acts on the kidney to decrease urine calcium, increase mine phosphate, and increase the conversion of 25-OH-vitamin D to l,25-(OH)2-vitamin D. PTH acts on bone acutely to increase bone resorption and thus release skeletal calcium into the circulation. However, due to the coupling of bone resorption and bone formation, the longer-term effect of increased PTH secretion is to increase both bone resorption and bone formation. 

Osteoporosis is a common condition, in which bone density is decreased as a consequence of an imbalance between bone formation (osteoblast) and bone loss (osteoclast). This leads to fragile bones, which are at an increased risk for fractures. The term porosis means spongy, which describes the large holes seen in these bones. 

Supplementation with high doses of vitamin K1 (1 mg/day for 14 days) or MK-4 (45 mg/day) resulted in decreased levels of undercarboxylated osteocalcin and increase of bone formation markers and in a significant reduction in bone loss, respectively. Using such high doses, any kind of effects besides vitamin K can not yet be ruled out and have to be further elucidated by long term studies. An overview can be found in a review by Palacios [4]. 

The most dramatic consequence of sHPT is alterations in bone turnover and the development of ROD. Other complications of CKD can also promote ROD. Metabolic acidosis decreases bone formation and aluminum toxicity causes aluminum uptake into bone in place of calcium, weakening the bone structure. The pathogenesis of sHPT and ROD are depicted in Fig. 23-5. 

It is important to monitor vitamin D therapy aggressively to assure that PTH levels are not oversuppressed. Oversuppression of PTH levels can induce adynamic bone disease, which manifests as decreased osteoblast and osteoclast activity, decreased bone formation, and low bone turnover. 

Calcitonin. This hormone, which is also secreted from the thyroid gland, is synthesized by the parafollicular cells (C cells) located between the follicles. The primary effect of calcitonin is to decrease the blood levels of calcium and phosphate. The mechanism of action involves the direct inhibition of osteoclast activity, which decreases bone resorption. This results in less demineralization of the bone and therefore a decrease in the release of calcium and phosphate from the bone into the blood. Calcitonin has no direct effect on bone formation by osteoblasts. 

Glucocorticoids decrease bone formation through decreased proliferation and differentiation, and enhanced apoptosis of osteoblasts. They also increase bone resorption, decrease calcium absorption, increase renal calcium excretion, and result in secondary hyperparathyroidism. 

To test the bone formation rate and the activation frequency, Heaney and Draper (1997) carried out a comparative histomorphometric survey. Ten women received a 60-mg daily dose of raloxifene while 8 received a 0.625-mg daily dose of CEE. Biopsies carried out before and after 6 months of treatment revealed a decrease in both parameters, especially in the group treated with estrogens. 

Many other dietary factors have been reported to affect calcium bioavailability. Phytate, fiber, cellulose, uronic acids, sodium alginate, oxalate, fat (only in the presence of steatorrhea), and alcohol have been reported to decrease calcium bioavailability (15). Lactose and medium chain triglyceride increase it (15). FTuoride also affects calcium retention primarily by stimulating bone formation thereby decreasing calcium excretion (33-38). The effects of fluoride on calcium utilization have been variable (34,38,39). 

The polypeptide parathormone is released from the parathyroid glands when plasma Ca + level falls. It stimulates osteoclasts to increase bone resorption in the kidneys, it promotes calcium reabsorption, while phosphate excretion is enhanced. As blood phosphate concentration diminishes, the tendency of calcium to precipitate as bone mineral decreases. By stimulating the formation of vit D hormone, parathormone has an indirect effect on the enteral uptake of Ca + and phosphate. In parathormone deficiency, vitamin D can be used as a substitute that unlike parathormone, is effective orally. 

Osteoporosis is defined as a generalized decrease in bone mass (osteopenia) that affects bone matrix and mineral content equally, giving rise to fractures of vertebral bodies with bone pain, kyphosis, and shortening of the torso. Fractures of the hip and the distal radius are also commoa The underlying process is a disequilibrium between bone formation by osteoblasts and bone resorption by osteoclasts. 

Parathyroid hormone is a single-chain polypeptide of 84 amino acids which is produced in the parathyroid glands. It increases serum calcium and decreases serum phosphate. In bone it promotes resorption of calcium. It indirectly increases osteoclastic activity by promoting the action of osteoblasts. It has been shown that in low doses PTH may even increase bone formation without stimulating bone resorption. In the kidney PTH increases resorption of calcium and it increases excretion of phosphate. An other important activity in the kidney is the enhanced synthesis of 1,25-dihydroxyvitamin D. An increased serum calcium level inhibits PTH secretion and increased serum phosphate decreases free serum calcium and thus stimulates PTH secretion. 

Consumption of soy foods (providing 60mg/day isoflavones) for 12 weeks by postmenopausal women has been found to significantly decrease clinical risk factors for osteoporosis (short-term markers of bone turnover) including decreased urinary M-telopeptide excretion (bone resorption marker) and increased serum osteocalcin (bone formation marker). Furthermore, consumption of a soy isoflavone supplement containing 61.8 mg of isoflavones for 4 weeks by postmenopausal Japanese women significantly decreased excretion of bone resorption markers. ... 

Bone Calcium and phosphate resorption increased by high doses. Low doses may increase bone formation. Increased calcium and phosphate resorption by l,25(OH)2D bone formation may be increased by l,25(OH)2D and 24,25(OH)2D Decreased mineralization due to hypophosphatemia... 

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. 

Wang C, Eyre DR, Clark R, Kleinberg D, Newman C, Iranmanesh A, Veldhuis J, Dudley RE, Berman N, Davidson T, Barstow TJ, Sinow R, Alexander G, Swerdloff RS. Sublingual testosterone replacement improves muscle mass and strength, decreases bone resorption, and increases bone formation markers in hypo-gonadal men—a clinical research center study. J Clin Endocrinol Metab 1996 81(10) 3654-62. 

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