Resorption minerals

Bone Resorption The removal of mineralised bone by osteoclasts. Bone resorption, which is part of the bone remodelling process, includes the release of mineral (mostly calcium and phosphate) and subsequent proteolysis of organic matter (mostly collagen). 

Alendronate, etidronate, and risedronate act primarily on the bone by inhibiting normal and abnormal bone resorption. This results in increased bone mineral density, reversing the progression of osteoporosis. 

Under normal circumstances, the skeleton undergoes a dynamic process of bone remodeling. Bone tissue responds to stress and injury through continuous replacement and repair. This process is completed by the basic multicellular unit, which includes both osteoblasts and osteoclasts. Osteoclasts are involved with resorption or breakdown of bone and continuously create microscopic cavities in bone tissue. Osteoblasts are involved in bone formation and continuously mineralize new bone in the cavities created by osteoclasts. Until peak bone mass is achieved between the ages of 25 and 35, bone formation exceeds bone resorption for an overall increase in bone mass. Trabecular bone is more susceptible to bone remodeling in part owing to its larger surface area. 

Macdonald H, New S, Fraser W, Campbell M and Reid D. 2005. Low dietary potassium intakes and high dietary estimates of net endogenous acid production are associated with low bone mineral density in premenopausal women and increased markers of bone resorption in postmenopausal women. Am J Clin... 

The results of the fractionation model (Fig. 24.9) differ from the equilibrium model in two principal ways. First, the mineral masses can only increase in the fractionation model, since they are protected from resorption into the fluid. Therefore, the lines in Figure 24.9 do not assume negative slopes. Second, in the equi-... 

KOning A, Muhlbauer RC, Fleisch H (1988) Tumor necrosis factor alpha and interleukin-1 stimulate bone resorption in vivo as measured by urinary [3H]tetracycline excretion from prelabeled mice. J Bone Miner Res 3 621-627... 

Eriksen EF, Hodgson SF, Eastell R, Cedel SL, O Fallon WM, Riggs BL (1990) Cancellous bone remodeling in type I (postmenopausal) osteoporosis quantitative assessment of rates of formation, resorption, and bone loss at tissue and cellular levels. J Bone Miner Res 5 311-319... 

Fig. 14.3. The different anti resorptive substances have different effects on densitometric bone mineral density but similar impact on vertebral fracture incidence based on 1 Chesnut et al. 2000 2Ettinger et al. 1999 3 Harris et al. 1999 4Reginster et al. 2000 5 Black et al. 2000 6 Cummings et al. 1998...

Delmas PD, Seeman E (2004) Changes in bone mineral density explain little of the reduction in vertebral or non vertebral fracture risk with anti-resorptive therapy. Bone 34 599-604... 

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. 

Calcium is the major mineral component of bone and normal repair and remodelling of bone is reliant on an adequate supply of this mineral. Calcium uptake in the gut, loss through the kidneys and turnover within the body are controlled by hormones, notably PTH and 1,25 dihydroxy cholecalciferol (1,25 DHCC or 1,25 dihydroxy vitamin D3 or calcitriol). Refer to Figure 8.12 for a summary of the involvement of PTH and vitamin D3 in controlling plasma calcium concentration. These two major hormones have complementary actions to raise plasma calcium concentration by promoting uptake in the gut, reabsorption in the nephron and bone resorption. Other hormones such as thyroxine, sex steroids and glucocorticoids (e.g. cortisol) influence the distribution of calcium. 

These results indicated osteoporosis. In this condition, which often appears secondary to another pathology such as an endocrinopathy, chronic renal failure or following long term immobilization, bone architecture is normal hut its mass is reduced relative to its volume, that is there is normal mineralization hut the amount of osteoid matrix is reduced. Treatment is with bone resorption inhibitors such as the bisphosphonate group of drugs, for example alendronate. 

Flanagan AM, Chambers TJ. Dichloromethylenebisphosphonate (C12mbp) inhibits bone-resorption through injury to osteoclasts that resorb C12mbp-coated bone. Bone Miner 1989 6 33 3. 

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. 

Bisphosphonates structurally mimic endogenous pyrophosphate, which inhibits precipitation and dissolution of bone minerals. They retard bone resorption by osteoclasts and, in part, also decrease bone mineralizatioa Indications include tumor osteolysis, hypercalcemia, and Paget s disease. Qinical trials with etidronate, administered as an intermittent regimen, have yielded favorable results in osteoporosis. With the newer drugs clodronate, pamidronate, and alendronate, inhibition of osteoclasts predominates a continuous regimen would thus appear to be feasible. 

Resorption of the required mineral substances from food usually depends on the body s requirements, and in several cases also on the composition of the diet. One example of dietary influence is calcium (see p. 342). Its resorption as Ca is promoted by lactate and citrate, but phosphate, oxalic acid, and phytol inhibit calcium uptake from food due to complex formation and the production of insoluble salts. 

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