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The Effect of Gallium Nitrate on Healing of Vitamin D– and Phosphate–Deficient Rickets in the Immature Rat

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Abstract

The effect of gallium on rapid in vivo mineralization was studied in a rachitic rat model in which rickets were induced in immature rats then reversed (“healed”) with repletion of vitamin D and phosphate. Gallium was administered to selected groups of animals before and during the healing phase. In nonrachitic animals and rachitic animals before healing, the mineral content of diaphyseal and metaphyseal bone was increased, and the crystal size was decreased in those animals that received gallium compared with those that did not. Mineralization of the undermineralized osteoid appeared histologically normal by 72 hours in all animals. However, animals that received gallium both before and during the healing phase had less well-mineralized bones at 18 hours, and by 72 hours, they had lesser increases in osteocalcin and mineral content, which was associated with smaller crystal sizes, than did any animal that did not receive gallium at any time. Prior to the healing phase, the ratio of gallium to hydroxyproline in the metaphyses of rachitic animals was similar to that in nonrachitic animals. Likewise, this ratio did not change in the animals receiving gallium both before and during the healing phase. The ratio of gallium to calcium was higher in rachitic animals compared with controls, and this ratio lowered significantly by the end of the healing phase. Results may be explained in part by direct effect of gallium on the physical process of mineral formation during the rapid healing phase as well as by effects of gallium on osteoblasts and osteoclasts during the induction of rickets.

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References

  1. Warrell RP, Bockman RS, Coonley CJ, Isaacs M, Staszewski HJ (1984) Gallium nitrate inhibits calcium resorption from bone and is effective treatment for cancer-related hypercalcemia. J Clin Invest. 73:1487–1490

    Article  CAS  Google Scholar 

  2. Warrell RP, Isaacs M, Coonley CJ, Alcock N, Bockman RS (1985) Metabolic effects of gallium nitrate administered by prolonged infusion. Cancer Treat Rep. 69:653–655

    PubMed  Google Scholar 

  3. Warrell RP, Skelkos A, Alcock NW, Bockman RS (1986) Gallium nitrate for acute treatment of cancer-related hypercalcemia: clinicopharmacological and dose-response analysis. Cancer Res. 46:4208–4212

    PubMed  Google Scholar 

  4. Warrell RP, Alcock NW, Bockman RS (1987) Gallium nitrate inhibits accelerated bone turnover in patients with bone metastases. J Clin Oncol. 5:292–298

    Article  Google Scholar 

  5. Warrell RP, Isaacs M, Alcock NW, Bockman RS (1987) Gallium nitrate for treatment of refractory hypercalcemia from parathyroid carcinoma. Ann Int Med. 107:683–686

    Article  Google Scholar 

  6. Warrell RP, Israel R, Frisone M, Snyder T, Gaynor JJ, Bockman RS (1988) Gallium nitrate for acute treatment of cancer-related hypercalcemia. Ann Int Med. 108:669–674

    Article  Google Scholar 

  7. Warrell RP, Bosco B, Weinerman S, Levine B, Lane JM, Bockman RS (1990) Gallium nitrate for advanced Paget’s disease of bone: effectiveness dose-response analysis. Ann Int Med. 113:847–851

    Article  Google Scholar 

  8. Matkovic V, Apseloff G, Shepard DR, Gerber N (1990) Use of gallium to treat Paget’s disease of bone. A pilot study. Lancet. 335:72–75

    Article  CAS  Google Scholar 

  9. Hall TJ, Chambers TJ (1990) Gallium inhibits bone resorption by a direct effect on osteoclasts. Bone Miner. 8:211–216

    Article  CAS  Google Scholar 

  10. Repo MA, Bockman RS, Betts F, Boskey AL, Alcock NW, Warrell RP (1988) Effect of gallium on bone mineral properties. Calcif Tissue Int. 43:300–306

    Article  CAS  Google Scholar 

  11. Donnelly RE, Bockman RS, Doty SB, Boskey AL (1991) Bone particles from gallium-treated rats are resistant to resorption in vivo. Bone Miner. 12:167–179

    Article  CAS  Google Scholar 

  12. Lakatos P, Mong S, Stem PH (1991) Gallium nitrate inhibits bone resorption and collagen synthesis in neonatal mouse calvaria. J Bone Miner Res. 6:1121–1126

    Article  CAS  Google Scholar 

  13. Blair HC, Teitelbaum SL, Tan HL, Schlessinger PH (1992) Reversible inhibition of osteoclastic activity by bone-bound gallium. J Cell Biochem. 48:401–410

    Article  CAS  Google Scholar 

  14. Guidon PT Jr. Salvatori R, Bockman RS (1993) Gallium nitrate regulates rat osteoblast expressions of osteocalcin protein and mRNA levels. J Bone Miner Res. 8:103–112

    Article  CAS  Google Scholar 

  15. Bockman RS, Guidon PT Jr. Salvatori R, Kawaguchi A, Pan LC (1993) Gallium nitrate increases type I collagen and fibronectin mRNA and collagen protein levels in bone and fibroblast cells. Cell Biochem. 53:1–8

    Article  Google Scholar 

  16. Bockman RS, Boskey AL, Blumenthal NC, Alcock MW, Warrell RP (1986) Gallium increases bone calcium and crystallite perfection of hydroxyapatite. Calcif Tissue Int. 39:376–381

    Article  CAS  Google Scholar 

  17. Donnelly RE, Boskey AL (1988) Gallium inhibition of hydroxyapatite seeded growth. Calcif Tissue Int. 44:138–142

    Article  Google Scholar 

  18. Blumenthal NC, Cosma V, Levine S (1989) Effect of gallium on the in vivo formation, growth, solubility of hydroxyapatite. Calcif Tissue Int. 45:81–87

    Article  CAS  Google Scholar 

  19. Simon DR, Berman I, Howell DS (1973) Relationship of extracellular matrix vesicles to calcification in normal and healing rachitic epiphyseal cartilage. Anat Rec. 176:167–180

    Article  CAS  Google Scholar 

  20. Atkin I, Pita JC, Ornoy A, Agundez A, Castiglione G, Howell DS (1985) Effects of vitamin-D metabolites on healing of low phosphate, vitamin D-deficient induced rickets in rats. Bone. 6:113–123

    Article  CAS  Google Scholar 

  21. Reingardt TA, Horst RL, Orf JW, Hollis BWA (1984) Microassay for 1,25-dihydroxy vitamin D not requiring high performance liquid chromatography. J Clin Endocrinol Metab. 58:91–98

    Article  Google Scholar 

  22. Boskey AL (1985) Lipid changes in the bones of the healing vitamin D-deficient phosphate-deficient rat. Bone. 6:173–178

    Article  CAS  Google Scholar 

  23. Hutterer F, Singer EJ (1970) A modified method for hydroxyproline determination. Anal Chem. 32:556–558

    Article  Google Scholar 

  24. Willis JB (1960) The determination of metals in blood serum by atomic absorption spectroscopy. Calcium Spectrochim Acta. 16:259–272

    Article  CAS  Google Scholar 

  25. Cullity BD (1956) Elements of x-ray diffraction. Addison-Wesley, Reading, MA, pp 96–102

    Google Scholar 

  26. Lundy DR, Eanes ED (1973) An x-ray line broadening study of turkey leg tendon. Oral Biol. 18:813–826

    Article  CAS  Google Scholar 

  27. Jackson SA, Cartright AS, Lewis D (1978) The morphology of bone mineral crystals. Calcif Tissue Res. 25:217–225

    Article  CAS  Google Scholar 

  28. Gundberg CM, Hauschka PV, Lian JB, Gallop PM (1984) Osteocalcin: isolation, characterization, and detection. Methods Enzymol. 107:516–544

    Article  CAS  Google Scholar 

  29. Walters RW, Folienkirchen U, Fox J (1992) What is vitamin D deficiency? Proc Soc Exp Biol Med. 199:385–395

    Article  CAS  Google Scholar 

  30. Wakley GK, Garand J, Brown D, Szukalski BW, Bell NH, Turner RT (1992) Effects of gallium on bone in the rat. J Bone Miner Res. 7:11–20

    Article  CAS  Google Scholar 

  31. Boskey AL, Zeichek W, Guidon P, Doty SB (1993) Gallium nitrate inhibits alkaline phosphatase activity in a differentiating mesenchymal cell culture. Bone Miner. 20:179–192

    Article  CAS  Google Scholar 

  32. Schenk R, Merz WA, Muhlbaver R, Russel RGG, Fleisch H (1973) Effect of ethane-1-hydroxyl-1, 1-diphosphonate (EHPD) and dichloro-methylene diphosphonate (C12MDP) on the calcification and resorption of cartilage and bone in the tibial epiphyses of rats. Calcif Tissue Res. 11:196–214

    Article  CAS  Google Scholar 

  33. Adelman RJ, Jones KW, Donnelly R, Wright TM, Bockman RS (1990) Gallium localization and effect on mechanical bone strength. Trans Orthop Res Soc 15:415

    Google Scholar 

  34. Cournot-Witmar G, Bourdeau C, Lieberherr M, Thil CL, Pla-chot JJ, Enault G, Bourdon R, Baisan S (1987) Bone modelling in gallium nitrate-treated rats. Calcif Tissue Int. 40:270–275

    Article  Google Scholar 

  35. Glimcher MJ (1989) Mechanism of calcification: role of collagen fibrils and collagen-phosphoprotein complexes in vitro and in vivo. Anat Rec. 224:139–153

    Article  CAS  Google Scholar 

  36. Bachra BN, van Harskamp GA (1970) The effect of polyvalent metal ions on the stability of a buffer system for calcification in vitro. Calcif Tissue Res. 4:359–365

    Article  CAS  Google Scholar 

  37. Garside J (1982) Nucleation. In: Nancollas GH (ed) Biological mineralization and demineralization. Springer Verlag, Amsterdam, pp 23–25

    Chapter  Google Scholar 

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Acknowledgments

This work was supported by NIH Grant CA 38645. The authors would like to thank Ms. Alicia Yau, Mr. Michael Maresca, and Ms. Jean Kilfoyle for their technical assistance.

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Donnelly, R., Bockman, R., DiCarlo, E. et al. The Effect of Gallium Nitrate on Healing of Vitamin D– and Phosphate–Deficient Rickets in the Immature Rat. Calcif Tissue Int 53, 400–410 (1993). https://doi.org/10.1007/BF03549783

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