Paget's Disease of Bone

Singer, Frederick R.; Schiller, Alan L.; Pyle, Eleanor B.; Krane, Stephen M.

doi:10.1016/b978-0-12-068702-2.50011-8

Cited by 15 publications

(3 citation statements)

References 167 publications

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“…In Paget's disease, in which bone turnover is increased but tight coupling between bone formation and bone resorption is preserved (20) so that no net bone loss occurs, there was consistently marked elevation in circulating levels of osteocalcin, while Gla excretion remained normal. Recent evidence suggests that an increased circulating osteocalcin level reflects new synthesis of the protein (21).…”

Section: Discussionmentioning

confidence: 93%

Urinaryγ-Carboxyglutamic Acid and Serum Osteocalcin as Bone Markers: Studies in Osteoporosis and Paget’s Disease*

Gundberg

Lian

Gallop

et al. 1983

The Journal of Clinical Endocrinology & Metabolism

155

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Osteocalcin is a major bone matrix protein with high affinity for hydroxyapatite. This property is conferred by several residues of the calcium-binding amino acid gamma-carboxyglutamate (Gla), which requires vitamin K for its biosynthesis. Because this protein may play a role in the local control of calcium deposition or removal in mineralized tissue, we measured circulating osteocalcin levels and urinary excretion of its breakdown product, Gla, in patients with osteoporosis and Paget's disease. Studies were conducted either on a metabolic ward or in ambulatory patients. Diagnoses were established by clinical and laboratory findings, and were confirmed by histological examination in 19 of 26 patients with osteoporosis. Mean urinary Gla excretion was increased (P less than 0.001) in patients with osteoporosis by 50% above the normal mean; serum osteocalcin, however, was not significantly different from normal. In Paget's disease patients, this pattern was reversed; serum osteocalcin levels were increased 3-fold (P less than 0.001), while urinary Gla excretion was consistently normal, regardless of the extent or activity of the disease. These data demonstrate that measurements of urinary Gla and serum osteocalcin may provide important insights into the metabolic derangements in these and other bone disorders.

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Section: Discussionmentioning

confidence: 93%

Urinaryγ-Carboxyglutamic Acid and Serum Osteocalcin as Bone Markers: Studies in Osteoporosis and Paget’s Disease*

Gundberg

Lian

Gallop

et al. 1983

The Journal of Clinical Endocrinology & Metabolism

155

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“…In patients with very active disease, the increased metabolic activity of the affected bone is probably the main determinant of uptake (Harink et al 1987). In patients with less active disease, increased vascularity and the persistence of woven bone with its increased surface to volume ratio are likely to be the most important variables determining the increase in DPS (Galasko 1975;Singer et al 1978). Serum alkaline phosphatase and urinary hydroxyproline are accepted indicators of osteoblastic and osteoclastic activity, respectively (Kanis and Gray 1987).…”

Section: Discussionmentioning

confidence: 99%

The diphosphonate space: a useful quantitative index of disease activity in patients undergoing hexamethylene diphosphonate (HMDP) bone imaging for Paget's disease

Evans¹,

Perkins²,

Wastie³

et al. 1991

Eur J Nucl Med

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Comparison between the plasma levels of intravenously injected technetium 99m hexamethylene diphosphonate (99mTc-HMDP) and chromium 5~ ethylene diamine tetra-acetic acid (51Cr-EDTA) reflects the uptake of diphosphonate into bone (the diphosphonate space). This can be used as an index of skeletal function in metabolic bone disease. In a series of 49 patients with Paget's disease the diphosphonate space (DPS) correlated well with other indicators of disease activity such as alkaline phosphatase and urinary hydroxyproline levels. The DPS is a good predictor of the volume of skeletal involvement as estimated from bone images. The DPS also provides a sensitive indicator of response to treatment with intravenously administered bisphosphonate. The DPS is simple to perform and is a useful adjunct to routine bone imaging.

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“…Its biological effect is to reduce bone resorption, inhibiting the function of osteoclasts present in bone and decreasing generation of osteoclasts from precursors) 75,87,88] Porcine calcitonin was firstly used in the treatment of Paget's disease. Its biological effect is to reduce bone resorption, inhibiting the function of osteoclasts present in bone and decreasing generation of osteoclasts from precursors) 75,87,88] Porcine calcitonin was firstly used in the treatment of Paget's disease.…”

Section: Calcitoninmentioning

confidence: 99%

Management of Osteoporosis and Paget??s Disease

et al. 1994

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Osteoporosis is a major public health problem occurring primarily among the postmenopausal population. Osteoporosis is a preventable disease, but despite several advances in its prevention, treatment of the established disease to date remains a major challenge to be managed by primary care physicians. Stabilisation of bone mass and prevention of falls are of paramount importance in any therapeutic programme for osteoporotic patients with established vertebral fractures. Drug therapy for osteoporosis can be divided operationally into 2 main categories: those that inhibit bone resorption, and thus reduce bone turnover, and those that stimulate bone formation, exerting an anabolic effect. Therapeutic agents that inhibit bone remodeling would appear to be best suited to those patients with high turnover osteoporosis (about 30%). Included in this category are calcium, vitamin D and its metabolites, gonadal steroids, calcitonin, ipriflavone and bisphosphonates. Although estrogen replacement therapy has been proven to be effective in older females, calcitonin appears to be the treatment of choice for this population since it stabilises or increases bone mass and also has reported analgesic properties. Drugs that stimulate bone remodeling or bone formation would be best suited to patients with low turnover osteoporosis (about 70%). The agent in this class that is widely used is sodium fluoride. New therapies include intermittent injections of synthetic parathyroid hormone, and cyclic bisphosphonates to activate then depress resorption and formation. Any attempts to stabilise the skeleton with any drug regimen must be accompanied by an adequate calcium supply, i.e. 1200 to 1500 mg/day). The theoretical basis of tailoring treatment for osteoporosis to the underlying histology has not yet been fully proven, but there is increasing experimental support to this approach. Drugs that inhibit bone turnover, such as calcitonin, appear to be effective in increasing bone mass for 1.5 to 2 years, about the time it would take to replenish the remodeling space in a patient with high turnover osteoporosis. In contrast, although bone mass appears to increase for as long as 5 years in patients treated with sodium fluoride, there has been no consistent reduction in occurrence of vertebral or hip fractures. Paget' disease of bone is a focal disorder of the skeleton characterised by excessive resorption and subsequently disorganised formation of bone. The aetiology of the disease is unknown. Paget's disease may be mono-ostotic or polyostotic; pain and bone deformities due to enlargement of skeletal segments represent the main clinical aspects. However, in many patients the disease may be asymptomatic.(ABSTRACT TRUNCATED AT 400 WORDS)

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Paget's Disease of Bone

Cited by 15 publications

References 167 publications

Urinaryγ-Carboxyglutamic Acid and Serum Osteocalcin as Bone Markers: Studies in Osteoporosis and Paget’s Disease*

Urinaryγ-Carboxyglutamic Acid and Serum Osteocalcin as Bone Markers: Studies in Osteoporosis and Paget’s Disease*

The diphosphonate space: a useful quantitative index of disease activity in patients undergoing hexamethylene diphosphonate (HMDP) bone imaging for Paget's disease

Management of Osteoporosis and Paget??s Disease

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