Abstract
We report 23 prospective studies on 18 maintenance dialysis patients in whom we measured skeletal mineralization rate (m) using 47Ca, analyzed by the expanding pool model, and compared it with the histologic bone formation rate (bfr), volume referent, estimated on tetracycline-labeled iliac crest bone. The patients showed a spectrum of bone disease types including adynamic bone, aluminum-related osteomalacia, and various degrees of secondary hyperparathyroidism. The mean width between double labels, on which mineral apposition rate depended, was estimated using a simple formula relating area to perimeter for each feature enclosed by the labels. Values for m ranged from 0 to 155 mmol calcium per day and for bfr from 0 to 124% per year. There was close correlation between m and bfr (r=0.976), serum alkaline phosphatase (r=0.968), and serum immunological parathyroid hormone (iPTH) (r=0.868). When the volumetric bfr was converted to mass units and applied to the whole skeleton, using literature values for mineral density and cortical and trabecular mass, there was close agreement between the histologic and isotopic estimates of m (r=0.959). The results validate the two methods and suggest they are interchangeable. However, use of a rigorous method to determine bfr appears to be essential.
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Parfitt M, Rao DS, Stanciu J, Villaneuva AR, Kleerekoper M, Frame B (1986) Irreversible bone loss in osteomalacia. J Clin Invest 76:2403–2412
Reeve J, Arlot ME, Chavassieux PM, Edouard C, Green JR, Hesp R, Tellez M, Meunier PJ (1987) The assessment of bone formation rate in osteoporosis: a comparison between tetracycline-based iliac crest histomorphometry and whole body 85Sr kinetics. J Bone Miner Res 2:479–489
Lee RW, Marshall JH, Sissons HA (1965) Calcium accretion and bone formation in dogs. J Bone Joint Surg 47B:157–180
Miravet L, Matrajt H, Bordier P, Tun S, Gruson M, Hioco D (1969) Correlation between biochemical kinetic and histological measurements in hyperparathyroidism. Proc Roy Soc Med 62: 241–242
Lauffenburger T, Olah AJ, Dambacher MA, Guncago J, Lentner C, Haas HG (1977) Bone remodeling and calcium metabolism. A correlated histomorphometric, calcium kinetic, and biochemical study in patients with osteoporosis and Paget's disease. Metabolism 26:589–605
Reeve J, Arlot M, Bernat M, Charhon S, Edouard C, Slovik D, Vismans FJE, Meunier PJ (1981) Calcium-47 kinetic measurements of bone turnover compared to bone histomorphometry in osteoporosis: the influence of human parathyroid fragment therapy. Metab Bone Dis Rel Res 3:23–30
Charles P, Erikson EF, Mosekilde L, Melsen F, Jensen FT (1987) Bone turnover and balance evaluated by a combined calcium balance and 47calcium kinetic study and dynamic histomorphometry. Metabolism 36:1118–1124
Cochran M, Stephens E (1983) Isotopic bone mineralisation rates in maintenance dialysis patients. J Lab Clin Med 102:324–331
Burkinshaw L, Marshall DH, Oxby CB, Spiers FW, Nordin BEC, Young MM (1969) Bone turnover model based on a continuously expanding pool. Nature 222:146–148
Marshall DH (1976) Calcium, phosphate and magnesium metabolism. In: Nordin BEC (ed) Churchill Livingstone, Edinburgh, London, New York, pp 278–281
Schenk RW (1965) Zur histologischen Verarbeitung von unentkalkten Knochen. Acta Anat 60:3–19
Buchanan MRC, Ihle BU, Dunn CM (1981) Haemodialysisrelated osteomalacia: a staining method to demonstrate aluminum. J Clin Pathol 34:1352–1354
Weinstein RS (1992) Disorders of bone and mineral metabolism. In: Coe FL, Favus MJ (eds) Raven Press, New York pp 455–474
Delling G, Leuhmann H (1980) Correlation of static and dynamic histomorphometric data in secondary hyperparathyroidism. Metab Bone Dis Rel Res 2s:339–348
Foldes J, Shih MS, Parfitt AM (1990) Frequency distribution of tetracycline-based measurements: implications for the interpretation of bone formation indices in the absence of doublelabeled surfaces. J Bone Miner Res 5:1063–1067
Weibel ER (1969) Stereological principles for morphometry in electron microscopy. Int Rev Cytol 26:235–302
Ibsen KH, Urist MR (1964) The biochemistry and physiology of the tetracyclines with special reference to mineralized tissues. Clin Orthop 32:143–169
Day ST, Crouthamel WG, Martinelli LC, Ma JK (1978) Mechanism of fluorometric analysis of tetracycline involving metal complexation. J Pharmacol Sci 67:1518–1523
Sherrard DJ, Baylink DJ, Werdegal JE, Maloney NA (1974) Quantitative histological studies on the pathogenesis of uremic bone disease. J Clin Endocrinol Metab 39:119–135
Charles P, Jensen FT, Moskilde L, Hansen HH (1983) Calcium metabolism evaluated by 45Ca kinetics: estimation of dermal calcium loss. Clin Sci 65:415–422
Frost HM (1969) Tetracycline-based histological analysis of bone remodeling. Calcif Tissue Res 3:211–237
Frost HM (1963) Bone remodeling dynamics. Charles C Thomas, Springfield, IL
Merz WA, Schenk RW (1970) Quantitative structural analysis of human cancellous bone. Acta Anat 75:54–66
Malluche HH, Sherman D, Meyer W, Massry SG (1982) A new semi-automated method for quantitative static and dynamic bone histology. Calcif Tissue Int 34:439–448
Frost HM (1983) Bone histomorphometry: choice of marking agent and labeling schedule. In: Recker RR (ed) Bone histomorphometry: techniques and interpretation. CRC Press, Boca Raton, FL, p 44
Boyce BF (1990) Bone biopsy and histomorphometry. In: Stevenson Wright JC (ed) New techniques in metabolic bone disease. London Boston Sydney, pp 110–131
Parfitt AM (1983) Stereological basis of bone histomorphometry: theory of quantitative microscopy. In: Recker RR (ed) Bone histomorphometry: techniques and interpretation. CRC Press, Boca Raton, FL, p 61
Kimmel DB, Jee WSS (1983) Measurement of area, perimeter and distance: details of data collection in bone histomorphometry. In: Recker RR (ed) Bone histomorphometry: techniques and interpretation. CRC Press, Boca Raton, FL, p 101
Frost HM (1980) Resting seams: on and off in lamellar boneforming centers. Metab Bone Dis Rel Res 2s:167–170
Birkenhager-Frenkel DH, Birkenhager JC (1985) Bone appositional rate and percentage of double and singly labelled surfaces: comparison of data from 5 μm and 20 μm sections. Bone 6:221–229
Horsman A (1976) Calcium, phosphate and magnesium metabolism. In: Nordin BEC (ed) Churchill Livingstone, Edinburgh, London, New York, p 361
Parfitt AM (1983) The physiological and clinical significance of bone histomorphometric data. In: Recker RR (ed) Bone histomorphometry: techniques and interpretation. CRC Press, Boca Raton, FL, pp 145–166
Bergmann P, Paternot T, Schoutens A (1983) Regional measurements of bone calcium accretion rate and exchangeable pool with a whole-body counter: method and studies in subjects without bone disease. Calcif Tissue Int 35:21–28
Lindergard B, Gullstrand P, Rydmarker S, Tibblin S (1977) Clinical evaluation of bone-densitometry in patients with final renal insufficiency operated for hyperparathyroidism. Scand J Urol Nephrol 11:59–67
Heaf JG, Nielson LP, Mogensen NB (1983) Use of bone mineral content determination in the evaluation of osteodystrophy among hemodialysis patients. Nephron 35:103–107
Pellegrino ED, Biltz RM (1965) the composition of human bone in uremia: observations on the reservoir function of bone and demonstration of a labile fraction of bone carbonate. Medicine 44:397–418
Prager PJ, Ritz E, Krempien B, Bommer J (1975) Roentgenological findings in the hand skeleton of patients on maintenance hemodialysis. In: Maiorca R, Lindholm T (eds) Opuscula medico-technica lundisa. XVI Garda meeting on short dialysis and uremic osteodystrophy. Rahms, Lund, pp 154–168
Cochran M (1981) Aspects of renal bone disease. Australian N Z J Med (suppl) 11:33–37
Denney JD, Sherrard DJ, Nelp WB, Chesnut CH, Baylink DJ (1973) Total body calcium and long-term calcium balace in chronic renal disease. J Lab Clin Med 82:226–240
Cochran M, Platts MM, Moorhead PJ, Buxton A (1981) Spontaneous hypercalcemia in maintenance dialysis patients: association with atypical osteomalacia and fractures. Min Electrolyte Metab 5:280–286
Wergedal JE, Baylink DJ (1974) Electron microprobe measurements of bone mineralisation rate in vivo. Am J Physiol 226:345–352
Armstrong WD, Singer L (1965) Composition and constitution of the mineral phase of bone. Clin Orthop 39:179–190
Milne-Thomson LM (1950) Jacobian elliptical function tables. Dover Publications Inc., New York
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Cochran, M., Neville, A. & Marshall, E.A. Comparison of bone formation rates measured by radiocalcium kinetics and double-tetracycline labeling in maintenance dialysis patients. Calcif Tissue Int 54, 392–398 (1994). https://doi.org/10.1007/BF00305526
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DOI: https://doi.org/10.1007/BF00305526