Histomorphometric changes in trabecular bone of renal failure patients treated with calcifediol

Frost, Harold M.; Griffith, D. L.; Jee, Webster S. S.; Kimmel, Donald B.; McCandlis, R.P.; Teitelbaum, Steven L.

doi:10.1016/0221-8747(81)90011-4

Cited by 45 publications

(12 citation statements)

References 21 publications

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“…The converse has been reported in dialysis patients treated with vitamin D when repeated bone biopsies were studied. Kaye et al [30] observed a decrease of TBV in 3 patients with severe osteitis fibrosa and osteosclerosis after dihydrotachysterol therapy, and Frost et al [31] documented a significant decrease of TBV in 24 patients with osteitis fibrosa after 17 weeks of therapy with calcifediol, which approached pretreatment values after 86 weeks of therapy. So, it is reasonable to suggest that the noninvasive assessment of spinal bone mass by CT, which is closely correlated with TBV in the bone biopsy, may be of help in the follow-up of hyper parathyroid bone disease of uremia, once the diagnosis has been established.…”

Section: Discussionmentioning

confidence: 99%

Comparison of Histomorphometry and Computerized Tomography of the Spine in Quantitating Trabecular Bone in Renal Osteodystrophy

Torres

Lorenzo²,

González-Posada

1986

Nephron

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Computerized tomography (CT) has the advantage of allowing the isolation of trabecular bone of the axial skeleton, which is the more sensitive to metabolic changes. By means of single-energy X-ray CT we have devised a method for assessing trabecular bone mass (TBM) at L-4 vertebral body, which has an acceptable reproductibility (CV = 2.76%). Normal values where obtained after studying 29 normal individuals from both sexes and different ages. In order to know if the method is accurate, TBM was assessed in 17 patients (6 with creatinine clearance < 6 ml/min and 11 on chronic hemodialysis), and in all of them the results were compared with the histomorphometry of the iliac crest bone biopsy. TBM assessed by CT correlated with trabecular bone volume (TBV; mineralized bone + osteoid) (r = 0.82; p < 0.001) and this correlation was not improved after adding the volume of marrow fibrosis to TBV. TBM assessed by CT also correlated with mineralized bone volume but at a lower level of significance (r = 0.72 ;p = 0.001), and no correlation was found with relative osteoid volume alone. These findings suggest that final CT value is an integral of mineralized bone and osteoid but with a higher influence of mineralized bone. Osteomalacia and osteitis fibrosa were seen in situations of normal, decreased, or increased TBM assessed by CT, although the 2 patients with severe osteosclerosis suffered osteomalacia. We conclude that the assessment of TBM by CT at the axial skeleton of uremic patients has an acceptable reproducibility and accuracy. Its potential role in the management of renal osteodystrophy by noninvasive means must be stablished with repetitive studies in the same subjects, as is suggested by preliminary reports.

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Section: Discussionmentioning

confidence: 99%

Comparison of Histomorphometry and Computerized Tomography of the Spine in Quantitating Trabecular Bone in Renal Osteodystrophy

Torres

Lorenzo²,

González-Posada

1986

Nephron

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“…A metaphyseal area (about 2 x 2.8 mm) ofthe microradiographs ofthe proximal tibia was analyzed by using the same procedure as for the trabecular bone ofthe proximal tibial epiphysis. The mineral apposition rate (in micrometers per day) ofthe metaphyseal trabeculae (lower secondary spongiosa region only) was determined by measuring the distances between double labels by ultraviolet microscopy of30-gum unstained and stained sections (11,17,18). Lastly, the occurrence of primary spongiosa was graded as present (+), partially present (±), or absent (0).…”

Section: Methodsmentioning

confidence: 99%

Excessive mineralization with growth plate closure in rats on chronic warfarin treatment.

Price¹,

Williamson²,

Haba³

et al. 1982

Proc. Natl. Acad. Sci. U.S.A.

245

104

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Rats maintained for 8 months on a level of warfarin sufficient to decrease the vitamin K-dependent protein of bone (bone Gla protein) to 2% ofnormal have an excessive mineralization disorder characterized by complete fusion of the proximal tibial growth plate and cessation of longitudinal growth. The general features of this abnormality resemble the fetal warfarin syndrome in humans, a disorder also characterized by excessive mineralization of the growth plate. These excessive mineralization disorders may be caused by the decreased levels of bone Gla protein, a protein that potently inhibits mineralization in vitro.The metabolism of vitamin K presents several intriguing problems in vertebrate physiology and biochemistry. One of the most interesting ofthese is the role ofvitamin K in systems other than blood coagulation. The classical approach to the analysis ofvitamin K physiology has been the study ofdefects in vitamin K-deficient animals. Such studies have established that the first consequence of acute vitamin K deficiency is bleeding and death due to the synthesis of abnormal forms of blood coagulation factors such as prothrombin and factors VII, IX, and X. It is now known that the abnormality in these factors is the absence of 'y-carboxyglutamate (Gla), a Ca2" binding amino acid whose post-translational synthesis from glutamate requires vitamin K (1, 2).Our primary interest over the past several years has been the function of bone Gla protein (BGP), a 49-residue protein of known structure (3, 4) which is numerically one of the 10 most abundant proteins in a typical vertebrate (5,6). To analyze the function ofthis protein in bone metabolism we developed a simple protocol by which rats can be maintained on the vitamin K antagonist warfarin without problems due to bleeding (7). In previous studies we found that animals maintained from birth to 2 months of age on this protocol grow normally and have normal bone structure and mineralization in spite of bone levels of BGP which are only 2% of normal (7).We report here the discovery of excessive mineralization with growth plate closure in the proximal tibia ofrats maintained on warfarin from birth to 8 months of age. MATERIALS AND METHODSMaintenance of Animals on Warfarin. Simonsen albino rats (Sprague-Dawley-derived, Simonsen Laboratories, Gilroy, CA) were maintained from birth to 8 months of age on daily dosages ofwarfarin and vitamin K1 as described (7). To facilitate comparisons, the 10 control rats were selected from litters born at the same time as experimental animals and received daily doses of saline and vitamin K1 (7). Both experimental and control groups had seven male and three female rats. None of the 10 experimental rats chosen at birth for this study showed signs of bleeding or ill health over the 8 months of the experiment. As reported (7), the weight gain ofexperimental and control rats was identical up to 90 days ofage. At8 months ofage the average weights were 402 g for the male and 237 g for the female experimental rats and 455 g for t...

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“…Only trabecular bone was evaluated. The sections were stained according to Goldner [14] and the follow ing variables measured: trabecular volume (percent of total bone tissue volume, no osteoid volume included), normal 9.6-21.4; oste oid surface (percent of trabecular surface), normal less than 12; osteoid seam width index (ratio of the osteoid volume to the osteoid surface [15]), normal less than 1.7; osteoclast activity (number of osteoclasts per square millimeter of total surface [16]), normal less than 0.12.…”

Section: Methodsmentioning

confidence: 99%

Studies of Bone Morphology, Bone Densitometry and Laboratory Data in Patients on Maintenance Hemodialysis Treatment

Lindergård

Johnell

Nilsson

et al. 1985

Nephron

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Bone morphological parameters of renal osteodystrophy such as abundance of osteoid surface, osteoid seam width index, calcification fronts, osteoclast activity and trabecular bone volume were studied in 71 patients on maintenance hemodialysis and compared with bone densitometry, laboratory and clinical data. Increased osteoclast activity (hyperparathyroidism) was by far the most common bone morphological finding. Patients with chronic pyelonephritis or polycystic kidney disease had more than double the amount of osteoid than patients with chronic glomerulonephritis. The trabecular bone volume seemed to be increased in most patients in contrast to the cortical bone volume which was decreased, judged from bone densitometry and previously from X-ray. Despite that patients with polycystic kidney disease were older, their trabecular volume was larger than in patients with glomerulonephritis. The bone mineral content evaluated by bone densitometry was low in most patients, and more associated with bone morphological signs of osteomalacia than with secondary hyperparathyroidism. Serum phosphate (S-Po₄) and serum parathyroid hormone (S-PTH) seemed to discriminate better between osteomalacia and secondary hyperparathyroidism than serum alkaline phosphatase (S-Alk. phosph.), which was elevated in both groups. Patients who had been bilaterally nephrectomized were no more abnormal than other patients, and they had lower S-Alk. phosph. The abundance of osteoclasts was found to be a predictor of future development of clinical secondary hyperparathyroidism.

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Histomorphometric changes in trabecular bone of renal failure patients treated with calcifediol

Cited by 45 publications

References 21 publications

Comparison of Histomorphometry and Computerized Tomography of the Spine in Quantitating Trabecular Bone in Renal Osteodystrophy

Comparison of Histomorphometry and Computerized Tomography of the Spine in Quantitating Trabecular Bone in Renal Osteodystrophy

Excessive mineralization with growth plate closure in rats on chronic warfarin treatment.

Studies of Bone Morphology, Bone Densitometry and Laboratory Data in Patients on Maintenance Hemodialysis Treatment

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