Bone turnover

Bone turnover Skeletal turnover Skeletal metabolism Bone remodelling... 

OPG has been shown to reduce bone turnover in postmenopausal women. More recently, Denusomab, an anti-RANKL mAb, has been tested for its ability to increase BMD and to reduce bone turnover. Results were promising and clinical phase III studies with fracture endpoints are presently under way. 

Most of the studies are cross-sectional, population studies in Japanese or Chinese pre- or postmenopausal women, investigating the correlation between dietary intake of soy products and measurements of BMD or biomarkers of bone turnover (Table 6.1). Several studies showed a positive correlation between high intake of soy products and improved BMD, especially at the... 

Table 6.1 Cross-sectional, population studies based on dietary intake of soy products and bone mineral density (BMD) or biomarkers of bone turnover...

Arjmandi et al., 1998a,b 95 d old OVX rats 35 d casein diet after OVX, then 65 d soy protein with isoflavones (9 mg/d) No significant effect of soy protein in reversal of bone loss, assessed by BMD. Soy induced femoral lGF-1 mRNA and some increases in bone turnover markers... 

Harrison et al., 1998 10 week old OVX rats low calcium diet treatment starts 2 weeks after OVX Soy protein with isoflavones (6 mg/d) for 4 weeks Reduced bone loss (higher bone weight, higher calcium content) but no decrease of markers of bone turnover for the soy group... 

Picherit et al., 2001 7 month old OVX adult rats 3 doses of isoflavone extract (20, 40, 80 mg/kg body wt/d) for 91 d Isoflavones reversed femoral failure load, total femoral, diphyseal or metaphyseal BMDs and normalized bone turnover markers induced by OVX. Optimal dose without uterotrophic effect was 40 mg/kg body wt... 

PICHERIT C, BENNETAU-PELISSERO C, CHANTERANNE B, LEBECQUE P, DAVICCO M-J, BARLET J-P and COXAM V (2001a) Soybean isoflavones dose-dependently reduce bone turnover but do not reverse estabhshed osteopenia in adult ovariectomized rats. JNutr 13 E 723-728. 

WANGEN K E, DUNCAN A M, MERZ-DEMLOW B E, XU X, MARCUS R, PHIPPS W R, KURZER M S (2000) Effects of soy isoflavones on markers of bone turnover in premenopausal and postmenopausal women. J Clin Endocrin Metab 85(9), 3043-8. 

It has been shown that in postmenopausal women habitually high intakes of dietary isoflavones are associated with higher bone mineral density (BMD) values at both the spine and hip region (Mei et al, 2001). It is conceivable that an isoflavone-rich diet may help to reverse the state of secondary hyperparathyroidism associated with estrogen withdrawal and hence lower the rate of bone turnover in postmenopausal women, thus reducing the risk of osteoporosis (Valtuena et al, 2003). Phytoestrogens could be used as natural SERMs (Brzezinski and Debi, 1999) and some studies (Setchell, 2001 and refs therein) support such an idea since the molecular targets of... 

With investigations of phytochemicals and functional foods, the outcome measure is generally going to be a biomarker of disease, such as serum cholesterol level as a marker of heart disease risk, or indicators of bone turnover as markers of osteoporosis risk. Alternatively, markers of exposure may also indicate the benefit from a functional food by demonstrating bioavailability, such as increased serum levels of vitamins or carotenoids. Some components will be measurable in both ways. For instance, effects of a folic acid-fortified food could be measured via decrease in plasma homocysteine levels, or increase in red blood cell folate. 

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. 

Parathyroidectomy is a treatment of last resort for sHPT, but should be considered in patients with persistently elevated iPTH levels above 800 pg/mL (800 ng/L) that is refractory to medical therapy to lower serum calcium and/or phosphorus levels.39 A portion or all of the parathyroid tissue may be removed, and in some cases a portion of the parathyroid tissue may be transplanted into another site, usually the forearm. Bone turnover can be disrupted in patients undergoing parathyroidectomy whereby bone production outweighs bone resorption. The syndrome, known as hungry bone syndrome, is characterized by excessive uptake of calcium, phosphorus, and magnesium for bone production, leading to hypocalcemia, hypophosphatemia, and hypomagnesemia. Serum ionized calcium levels should be monitored frequently (every 4 to 6 hours for the first 48 to 72 hours) in patients receiving a parathyroidectomy. Calcium supplementation is usually necessary, administered IV initially, then orally (with vitamin D supplementation) once normal calcium levels are attained for several weeks to months after the procedure. 

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. 

Thiazide diuretics decrease urinary calcium excretion and may decrease bone turnover. However, their effects on bone mineral density and fracture rates have not been studied in controlled trials. Thiazide diuretics are not recommended solely for potential beneficial effects in osteoporosis. 

Subchondral bone undergoes metabolic changes, including increased bone turnover, that appear to be precursors to tissue destruction. The normally contiguous bony surface becomes fissured. Persistent use of the joint eventually results in loss of cartilage, permitting bone-to-bone contact that ultimately promotes thickening and eburnation of exposed bone. Microfractures may appear in subchondral bone, and osteonecrosis may develop beneath the surface. 

Bone remodeling The constant process of bone turnover involving bone resorption followed by bone formation. 

Renal osteodystrophy Altered bone turnover that results from sustained metabolic conditions that occur in chronic kidney disease, including secondary hyperparathyroidism, hyperphosphatemia, hypocalcemia, and vitamin D deficiency. 

These effects could not be directly related to estimated radiation dose or bone turnover rates (see... 

The Leggett Model simulates the age-dependence of lead kinetics on such factors as bone turnover rates, partitioning between soft tissues and excreta, removal half-times in liver, kidneys, and red blood cells, and the deposition fraction in brain. The model structure represents a compromise between biological realism and practical considerations regarding the quantity and quality of information available to determine parameter values (Leggett 1993). 

The toxicokinetics of lead in children appears to be similar to that in adults, with the exception of the higher absorption of ingested lead in children. Most of the lead body burden in both children and adults is in bone a slightly large fraction of the body burden in adults resides in bone (Barry 1975). The difference may reflect the larger amount of trabecular bone and bone turnover during growth trabecular bone has a shorter retention halftime for lead than does cortical bone (See Section 2.3.3 for details). 

Scholl TO Univ of Medical/Dental NJ-School of Osteopathic Medicine, Stratford, NJ This prospective study will allow the investigators to examine lead mobilization from bone turnover in stillgrowing, adolescent and mature mothers National Institute of Environmental Health Sciences... 

Marcus, R., Agents affecting calcification and bone turnover calcium, phosphate, parathyroid hormone, vitamin D, calcitonin, and other compounds, in Goodman and Gilman s The Pharmacological Basis of Therapeutics, 9th ed., Hardman, J.G. and Limbird, L.E., Eds., McGraw-Hill, New York, 1996, chap. 61. 

The skeleton consists of approximately 80 % cortical bone and 20 % trabecular bone, mainly in the axial skeleton. These amounts vary according to site and relate to the need for mechanical support. While trabecular bone accounts for the minority of total skeletal tissue, it is the site of greater bone turnover because its total surface area is greater than that of cortical bone. 

Antioxidants in fruits and vegetables including vitamin C and (3-carotene reduce oxidative stress on bone mineral density, in addition to the potential role of some nutrients such as vitamin C and vitamin K that can promote bone cell and structural formation (Lanham-New 2006). Many fruits and vegetables are rich in potassium citrate and generate basic metabolites to help buffer acids and thereby may offset the need for bone dissolution and potentially preserve bone. Potassium intake was significantly and linearly associated with markers of bone turnover and femoral bone mineral density (Macdonald and others 2005). 

In a study with 40 healthy men and women, average age 63.7 years, who were randomized to either an alkali diet (meat plus fruits and vegetables) or an acid diet (meat plus cereal grains) (Jajoo and others 2006), altering the renal net acid excretion over a period of 60 days affected several biochemical markers of bone turnover and calcium excretion. The acidity of the diet had a significant effect on increasing NTX, a urinary marker of bone breakdown, and increasing the amount of calcium excreted in the urine. 

Lin P-H, Ginty F, Appel L, Aickin M, Bohannon A, Gamero P, Barcaly D and Svetkey L. 2003. The DASH diet and sodium reduction improve markers of bone turnover and calcium metabolism in adults. 

Calcitonin is used clinically to treat hypercalcaemia associated with some forms of malignancy and Paget s disease. The latter condition is a chronic disorder of the skeleton in which bone grows abnormally in some regions. It is characterized by substantially increased bone turnover rates,... 

Bone loss occurs when bone resorption exceeds bone formation, usually from high bone turnover when the number and/or depth of bone resorption sites greatly exceed the rate and ability of osteoblasts to form new bone. 

Age-related osteoporosis occurs mainly because of hormone, calcium, and vitamin D deficiencies leading to accelerated bone turnover and reduced osteoblast formation. 

Major risk factors include current smoker, low body weight (<127 lb in postmenopausal women), history of osteoporotic fracture in a first-degree relative, and personal history of low-trauma fracture as an adult. Other independent risk factors include age, high bone turnover, low body mass index (<19 kg/m2), rheumatoid arthritis, and glucocorticoid use. Decision tools may help identify individuals who should undergo BMD testing, such as the Osteoporosis Risk Assessment Instrument and the Simple Calculated Osteoporosis Risk Estimation. 

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