Biochemical Markers of Bone Resorption Compared with Estimates of Bone Resorption from Radiotracer Kinetic Studies in Osteoporosis

Eastell, Richard; Colwell, A.; Hampton, Lance J.; Reeve, J.

doi:10.1359/jbmr.1997.12.1.59

Cited by 111 publications

(42 citation statements)

References 24 publications

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“…The NTx assay is clearly increased in primary hyperparathyroidism and returns to normal with effective treatment (Guo et al, 1996). Total deoxypyridinoline is the gold standard of bone resorption markers in that it is speci®c to bone, correlates well with estimates of bone resorption by calcium kinetics (Eastell et al, 1997) and is not affected by renal metabolism, unlike other crosslink forms (Colwell & Eastell, 1996). Previous studies have reported no change in free deoxypyridinoline (Karkkainen & Lamberg-Allardt, 1996) and no change (Zemel & Linkswiler, 1981;Calvo et al, 1990;Silverberg et al, 1986) or an increase in urinary hydroxyproline (Calvo et al, 1988;Bell et al, 1977).…”

Section: Discussionmentioning

confidence: 98%

Phosphate supplementation in young men: lack of effect on calcium homeostasis and bone turnover

et al. 1998

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Objective: To examine the effect of phosphate supplements on calcium homeostasis and bone turnover in young men. Design: Study 1 was a randomised, controlled, cross-over trial of 1000 mg elemental phosphate given for one week, with a standard diet of 800 mgad each of calcium and phosphorus. Study 2 was an escalating dose study of 0, 1000, 1500 and 2000 mgad elemental phosphate, each given for one week, with a standard diet of 1000 mgad each of calcium and phosphate. Setting: Northern General Hospital, Shef®eld. Subjects: Study 1, 10 healthy men ages 19±32 y. Study 2, 12 healthy men ages 19±38 y. Interventions: Sodium acid phosphate tablets each containing 500 mg elemental phosphorus (16.1 mmolad), given with meals. Results: Study 1, administration of 32.2 mmolad phosphorus resulted in a mean increase of 13.2 mmolad urinary phosphorus, a mean decrease of 1.1 mmolad urinary calcium, and a mean increase of 7 ngamL in serum intact PTH. There were no changes in serum phosphate, osteocalcin or urinary N-telopeptide excretion. Study 2, administration of 64.4 mmolad phosphorus resulted in a mean increase of 27.2 mmolad urinary phosphorus, a mean decrease of 2.4 mmolad urinary calcium, with no change in serum phosphate, PTH or urinary deoxypyridinoline. Conclusions: Phosphate supplementation of the diet does not affect bone turnover in young men.

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Section: Discussionmentioning

confidence: 98%

Phosphate supplementation in young men: lack of effect on calcium homeostasis and bone turnover

et al. 1998

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“…Bone constitutes the major pool of PYD and DPD cross-links. Although quantities of DPD have been detected in soft tissues such as the aorta and ligaments (42), the turnover of collagen in these tissues is very low, and thus urinary DPD can be considered to be a specific marker for bone-collagen degradation (43,44). Two studies have demonstrated the close association between urinary cross-link excretion and the rate of bone resorption, as determined by radioisotopic and histomorphometric measurements.…”

Section: Figure 10mentioning

confidence: 99%

A selective inhibitor of the osteoclastic V-H+-ATPase prevents bone loss in both thyroparathyroidectomized and ovariectomized rats

Visentin¹,

Dodds²,

Valente³

et al. 2000

J. Clin. Invest.

111

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IntroductionInhibitors of bone resorption can preserve bone mass and maintain normal bone architecture, thereby preventing fractures in later life (1).The bone-resorption process requires secretion of protons by the osteoclasts (2). This allows the dissolution of the bone mineral and the maintenance of the acidic environment required by proteolytic enzymes to degrade the bone matrix (3). Protons are extruded by a proton pump belonging to the class of vacuolar-type H + -ATPases (V-H + -ATPases (4) that is present in high concentration on the ruffled border (apical surface) of the resorbing osteoclast.The osteoclast V-H + -ATPase therefore represents a previously unexploited molecular target for the design of novel agents for reducing osteoclast activity. However, since V-H + -ATPase is an ubiquitous component of eukaryotic organisms and is the major electrogenic pump of endomembranes (5), the selective inhibition of the osteoclast V-H + -ATPase must be achieved in order to afford novel drugs that may constitute useful and safe agents for the treatment of osteoporosis and related osteopenic diseases.Bafilomycin A 1 , a potent and specific inhibitor of V-H + -ATPases (6), inhibits bone resorption both in vitro (7) and in vivo (8). However, since bafilomycin is not selective for any particular type of V-H + -ATPases, when administered to animals it inhibits all the essential V-H + -ATPases leading to systemic alteration of cellular physiology and to unacceptable toxicity (9). Recently, a novel class of small molecules endowed with potent osteoclast V-H + -ATPase inhibitory activity has been discovered (10), whose optimization resulted in (2Z,4E)-5-(5,6-dichloro-2-indolyl)-2-methoxy-N-(1,2,2,6,6-pentamethylpiperidin-4-yl)-2,4-pentadienamide (SB 242784; Figure 1) (11). The in vitro V-H + -ATPase inhibitory profile of SB 242784 has been reported previously (11). SB 242784 was a low-nanomolar inhibitor (IC 50 = 26.3 nM) of the bafilomycin-sensitive (vacuolar) Mg 2+ -ATPase in membrane preparations of osteoclasts obtained from egg-laying hens. In addition, SB 242784 was a very potent inhibitor of bone resorption (IC 50 = 3.4 nM) in an assay measuring the collagen fragments released from bone slices after a 48-hour incubation with human osteoclasts.In this paper we characterize further the biochemical and pharmacological actions of SB 242784 and demonstrate that it is highly selective for the V-H + -ATPase of human osteoclasts when compared with V-H + -ATPases from a number of other human tissues. Most importantly, we show that oral administration of SB 242784 reduces the retinoid-induced hypercalcemia in thyroparathyroidectomized (TPTX) rats and prevents the A potent and selective inhibitor of the osteoclastic V-H + -ATPase, (2Z,4E)-5-(5,6-dichloro-2-indolyl)-2-methoxy-N-(1,2,2,6,6-pentamethylpiperidin-4-yl) -2,4-pentadienamide (SB 242784), was evaluated in two animal models of bone resorption. SB 242784 completely prevented retinoid-induced hypercalcemia in thyroparathyroidectomized (TPTX) rats when administered orally ...

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“…(4) These cross-links are present in a minute amount in the tendon and aorta but absent from skin, an abundant source of type I collagen. (4) Urinary cross-link excretion, especially deoxypyridinoline, correlates with bone turnover in patients with vertebral osteoporosis (7,8) and fracture risk. (9,10) These markers are now being used to assess efficacy of treatment for metabolic bone diseases (11)(12)(13)(14)(15) and fracture risk.…”

Section: Introductionmentioning

confidence: 99%

Implant Design Affects Markers of Bone Resorption and Formation in Total Hip Replacement

Qureshi

Virdi

DiDonna

et al. 2002

Journal of Bone and Mineral Research

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Concentrations of the bone resorption markers pyridinoline and deoxypyridinoline and the bone formation marker osteocalcin were measured in 24-h urine collections from 30 subjects who underwent unilateral total hip replacements for monoarticular symptomatic osteoarthrosis and 10 controls. The patient groups were divided based on the femoral implant type (cemented cobalt alloy stem, cementless porous coated cobalt alloy stem, and cementless porous coated titanium alloy stem). Urine collections were performed before surgery and then at 3, 6, 12, 24, and 36 months. There were significant changes over time in the three patient groups for pyridinoline, deoxypyridinoline, and the ratio of osteocalcin to deoxypyridinoline (p < 0.01), but the control group values did not change over time. The resorption markers tended to peak at 3 months and the osteocalcin to deoxypyridinoline ratio was more variable, having depressed values in the cementless cobalt alloy group and elevated values in the other two groups compared with baseline. The cementless cobalt alloy group had higher resorption marker levels than the cemented cobalt alloy group at 6, 12, 24, and 36 months and higher levels than the cementless titanium alloy group at all postoperative times (p < 0.05). The osteocalcin to deoxypyridinoline ratio was lower in the cementless cobalt alloy group than in the cemented cobalt alloy group at 3, 6, and 24 months and the cementless titanium alloy group at 6, 12, and 24 months (p < 0.05). For the cemented cobalt chrome group, the baseline-normalized resorption marker values at 3 months and 6 months were correlated with the severity of radiographically assessed bone loss at 36 months (0.749 < r < 0.840; p < 0.05). For the cementless titanium alloy group, baseline-normalized osteocalcin/ deoxypyridinoline ratios at 3 months and 6 months were related inversely to radiographic bone loss at 36 months (0.687 < r < 0.749; p < 0.05). Thus, body fluid markers of bone metabolism change after total hip replacement. In addition, the changes in the marker concentrations were sensitive to implant design and were correlated with subsequent stress-shielding-induced bone loss. (J Bone Miner Res 2002;17:800 -807)

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Biochemical Markers of Bone Resorption Compared with Estimates of Bone Resorption from Radiotracer Kinetic Studies in Osteoporosis

Cited by 111 publications

References 24 publications

Phosphate supplementation in young men: lack of effect on calcium homeostasis and bone turnover

Phosphate supplementation in young men: lack of effect on calcium homeostasis and bone turnover

A selective inhibitor of the osteoclastic V-H+-ATPase prevents bone loss in both thyroparathyroidectomized and ovariectomized rats

Implant Design Affects Markers of Bone Resorption and Formation in Total Hip Replacement

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