Preservation and promotion of bone formation in the mandible as a response to a novel calcium-phosphate based biomaterial in mineral deficiency induced low bone mass male versus female rats
Kritika Srinivasan
Department of Biomaterials and Biomimetics, New York University College of Dentistry, 433 First Avenue, New York, New York, 10010
These authors contributed equally in this work and they both are the first authors of this manuscript.
Search for more papers by this authorDiana P. Naula
Department of Biomaterials and Biomimetics, New York University College of Dentistry, 433 First Avenue, New York, New York, 10010
These authors contributed equally in this work and they both are the first authors of this manuscript.
Search for more papers by this authorDindo Q. Mijares
Department of Biomaterials and Biomimetics, New York University College of Dentistry, 433 First Avenue, New York, New York, 10010
Search for more papers by this authorMalvin N. Janal
Department of Epidemiology and Health promotion, New York University College of Dentistry, 380 Second Avenue, Suite 301, New York, New York, 10010
Search for more papers by this authorRacquel Z. LeGeros
Department of Biomaterials and Biomimetics, New York University College of Dentistry, 433 First Avenue, New York, New York, 10010
Search for more papers by this authorCorresponding Author
Yu Zhang
Department of Biomaterials and Biomimetics, New York University College of Dentistry, 433 First Avenue, New York, New York, 10010
Correspondence to: Y. Zhang; e-mail: [email protected]Search for more papers by this authorKritika Srinivasan
Department of Biomaterials and Biomimetics, New York University College of Dentistry, 433 First Avenue, New York, New York, 10010
These authors contributed equally in this work and they both are the first authors of this manuscript.
Search for more papers by this authorDiana P. Naula
Department of Biomaterials and Biomimetics, New York University College of Dentistry, 433 First Avenue, New York, New York, 10010
These authors contributed equally in this work and they both are the first authors of this manuscript.
Search for more papers by this authorDindo Q. Mijares
Department of Biomaterials and Biomimetics, New York University College of Dentistry, 433 First Avenue, New York, New York, 10010
Search for more papers by this authorMalvin N. Janal
Department of Epidemiology and Health promotion, New York University College of Dentistry, 380 Second Avenue, Suite 301, New York, New York, 10010
Search for more papers by this authorRacquel Z. LeGeros
Department of Biomaterials and Biomimetics, New York University College of Dentistry, 433 First Avenue, New York, New York, 10010
Search for more papers by this authorCorresponding Author
Yu Zhang
Department of Biomaterials and Biomimetics, New York University College of Dentistry, 433 First Avenue, New York, New York, 10010
Correspondence to: Y. Zhang; e-mail: [email protected]Search for more papers by this authorAbstract
Calcium and other trace mineral supplements have previously demonstrated to safely improve bone quality. We hypothesize that our novel calcium-phosphate based biomaterial (SBM) preserves and promotes mandibular bone formation in male and female rats on mineral deficient diet (MD). Sixty Sprague–Dawley rats were randomly assigned to receive one of three diets (n = 10): basic diet (BD), MD or mineral deficient diet with 2% SBM. Rats were sacrificed after 6 months. Micro-computed tomography (µCT) was used to evaluate bone volume and 3D-microarchitecture while microradiography (Faxitron) was used to measure bone mineral density from different sections of the mandible. Results showed that bone quality varied with region, gender and diet. MD reduced bone mineral density (BMD) and volume and increased porosity. SBM preserved BMD and bone mineral content (BMC) in the alveolar bone and condyle in both genders. In the alveolar crest and mandibular body, while preserving more bone in males, SBM also significantly supplemented female bone. Results indicate that mineral deficiency leads to low bone mass in skeletally immature rats, comparatively more in males. Furthermore, SBM administered as a dietary supplement was effective in preventing mandibular bone loss in all subjects. This study suggests that the SBM preparation has potential use in minimizing low peak bone mass induced by mineral deficiency and related bone loss irrespective of gender. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1622–1632, 2016.
REFERENCES
- 1 National Osteoporosis Foundation. 54 Million Americans Affected by Osteoporosis and Low Bone Mass. Washington, D.C. 2014.
- 2 Osteoporosis Prevention, Diagnosis, and Therapy. NIH Consens Statement Online 2000 March 27-29; 17(1): 1–36.
- 3 Bonjour JP, Theintz G, Law F, Slosman D, Rizzoli R. Peak bone mass. Osteoporos Int 1994; 4: 7–13.
- 4 Mardon J, Trzeciakiewicz A, Habauzit V, Davicco MJ, Lebecque P, Mercier S, Tressol JC, Horcajada MN, Demigne C, Coxam V. Dietary protein supplementation increases peak bone mass acquisition in energy-restricted growing rats. Pediatr Res 2009; 66: 513–518.
- 5 Nieves JW, Formica C, Ruffing J, Zion M, Garrett P, Lindsay R, Cosman F. Males have larger skeletal size and bone mass than females, despite comparable body size. J Bone Miner Res 2005; 20: 529–535.
- 6 Young D, Hopper JL, Macinnis RJ, Nowson CA, Hoang NH, Wark JD. Changes in body composition as determinants of longitudinal changes in bone mineral measures in 8 to 26-year-old female twins. Osteoporos Int 2001; 12: 506–515.
- 7 Ho-Pham LT, Nguyen UD, Nguyen TV. Association between lean mass, fat mass, and bone mineral density: A meta-analysis. J Clin Endocrinol Metab 2014; 99: 30–38.
- 8 Ijuin M, Douchi T, Matsuo T, Yamamoto S, Uto H, Nagata Y. Difference in the effects of body composition on bone mineral density between pre- and postmenopausal women. Maturitas 2002; 43: 239–244.
- 9 Reid IR. Relationships among body mass, its components, and bone. Bone 2002; 31: 547–555.
- 10 Kribbs PJ, Smith DE, Chesnut CH III. Oral findings in osteoporosis. Part II: Relationship between residual ridge and alveolar bone resorption and generalized skeletal osteopenia. J Prosthet Dent 1983; 50: 719–724.
- 11 Erdogan O, Shafer DM, Taxel P, Freilich MA. A review of the association between osteoporosis and alveolar ridge augmentation. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007; 104: 738.e1–13.
- 12 Bollen A-M, Taguchi A, Hujoel PP, Hollender LG. Case-control study on self-reported osteoporotic fractures and mandibular cortical bone. Oral Surg Oral Med Oral Pathol Oral Radiol Endodontol 2000; 90: 518–524.
- 13 Sirimaharaj W, Pyungtanasup K. The epidemiology of mandibular fractures treated at Chiang Mai University Hospital: A review of 198 cases. J Med Assoc Thai 2008; 91: 868–874.
- 14 Zix J, Andreas SB, Olivier L, Nikola S, Hanna T, Tateyuki I. Incidence, aetiology and pattern of mandibular fractures in central switzerland. Swiss Med Wkly 2011; 141.
- 15 Becker W, Hujoel PP, Becker BE, Willingham H. Osteoporosis and implant failure: An exploratory case-control study. J Periodontol 2000; 71: 625–631.
- 16 Singhal S, Chand P, Singh BP, Singh SV, Rao J, Shankar R, Kumar S. The effect of osteoporosis on residual ridge resorption and masticatory performance in denture wearers. Gerodontology 2012; 29: e1059–e1066.
- 17 Holahan CM, Koka S, Kennel KA, Weaver AL, Assad DA, Regennitter FJ, Kademani D. Effect of osteoporotic status on the survival of titanium dental implants. Int J Oral Maxillofac Implants 2008; 23: 905–910.
- 18 Wells G, Cranney A, Peterson J, Boucher M, Shea B, Robinson V, Coyle D, Tugwell P. Risedronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women. Cochrane Database Syst Rev 2008(1): Cd004523.
- 19 Whitaker M, Guo J, Kehoe T, Benson G. Bisphosphonates for osteoporosis—Where do we go from here? N Engl J Med 2012; 366: 2048–2051.
- 20 Body JJ. How to manage postmenopausal osteoporosis? Acta Clin Belg 2011; 66: 443–447.
- 21 Suresh E, Pazianas M, Abrahamsen B. Safety issues with bisphosphonate therapy for osteoporosis. Rheumatology (Oxford) 2014; 53: 19–31.
- 22 Felson DT, Zhang Y, Hannan MT, Kiel DP, Wilson PW, Anderson JJ. The effect of postmenopausal estrogen therapy on bone density in elderly women. N Engl J Med 1993; 329: 1141–1146.
- 23 Colditz GA, Stampfer MJ, Willett WC, Hennekens CH, Rosner B, Speizer FE. Prospective study of estrogen replacement therapy and risk of breast cancer in postmenopausal women. JAMA 1990; 264: 2648–2653.
- 24 Ebeling PR. Clinical practice. Osteoporosis in men. N Engl J Med 2008; 358: 1474–1482.
- 25 Antonio Cilotti AF. Male osteoporosis and androgenic therapy: From testosterone to SARMs. Clin Cases Miner Bone Metab 2009; 6: 229–233.
- 26 Heaney RP. Calcium, dairy products and osteoporosis. J Am Coll Nutr 2000; 19: 83s–99s.
- 27 Bischoff-Ferrari HA, Dawson-Hughes B, Baron JA, Burckhardt P, Li R, Spiegelman D, Specker B, Orav JE, Wong JB, Staehelin HB, O'Reilly E, Kiel DP, Willett WC. Calcium intake and hip fracture risk in men and women: A meta-analysis of prospective cohort studies and randomized controlled trials. Am J Clin Nutr 2007; 86: 1780–1790.
- 28 Rude RK, Gruber HE. Magnesium deficiency and osteoporosis: Animal and human observations. J Nutr Biochem 2004; 15: 710–716.
- 29 Nielsen FH, Lukaski HC, Johnson LK, Roughead ZK. Reported zinc, but not copper, intakes influence whole-body bone density, mineral content and T score responses to zinc and copper supplementation in healthy postmenopausal women. Br J Nutr 2011; 106: 1872–1879.
- 30 Yamaguchi M. Role of nutritional zinc in the prevention of osteoporosis. Mol Cell Biochem 2010; 338: 241–254.
- 31 LeGeros RZLJ, Trautz OR, Shirra WP. Conversion of monetite, CaHPO4, to apatites: Effect of carbonate on the crystallinity and morphology of the apatite crystallites. Adv X-ray Anal 1971; 14: 57–66.
- 32 LeGeros RZ. Calcium phosphates in oral biology and medicine. Monogr Oral Sci 1991; 15: 1–201.
- 33 Mijares DQ. Synthetic Bone Mineral (SBM): Effect on Preventing Bone Loss Induced by Estrogen Deficiency in a Rat Model. New York: New York University; 2010. 83 p.
- 34 Sengupta P. A scientific review of age determination for a laboratory rat: How old is it in comparison with human age? Biomed Int 2011; 2: 81–89.
- 35 Jee WS, Yao W. Overview: Animal models of osteopenia and osteoporosis. J Musculoskelet Neuronal Interact 2001; 1: 193–207.
- 36 Bagi CM, Hanson N, Andresen C, Pero R, Lariviere R, Turner CH, Laib A. The use of micro-CT to evaluate cortical bone geometry and strength in nude rats: Correlation with mechanical testing, pQCT and DXA. Bone 2006; 38: 136–144.
- 37 Laib A, Barou O, Vico L, Lafage-Proust MH, Alexandre C, Rugsegger P. 3D micro-computed tomography of trabecular and cortical bone architecture with application to a rat model of immobilisation osteoporosis. Med Biol Eng Comput 2000; 38: 326–332.
- 38 Teo JCM, Si-Hoe KM, Keh JEL, Teoh SH. Correlation of cancellous bone microarchitectural parameters from microCT to CT number and bone mechanical properties. Mater Sci Eng C 2007; 27: 333–339.
- 39 Mijares D, Kulkarni A, Lewis K, Yao F, Xi Q, Tannous S, Dias R, LeGeros RZ. Oral bone loss induced by mineral deficiency in a rat model: Effect of a synthetic bone mineral (SBM) preparation. Arch Oral Biol 2012; 57: 1264–1273.
- 40 Vlasiadis KZ, Damilakis J, Velegrakis GA, Skouteris CA, Fragouli I, Goumenou A, Matalliotakis J, Koumantakis EE. Relationship between BMD, dental panoramic radiographic findings and biochemical markers of bone turnover in diagnosis of osteoporosis. Maturitas 2008; 59: 226–233.
- 41 Weat R, Astle, MJ., Beyer, WH. Handbook of Chemistry and Physics. Boca Raton, Florida: CRC Press Inca; 1987. p 88.
- 42 LeGeros RZ, Mijares D, Yao F, Tannous S, Catig G, Xi Q, Dias R, LeGeros JP. Synthetic bone mineral (SBM) for osteoporosis therapy: Part 1—Prevention of bone loss from mineral deficiency. Key Eng Mater 2008; 361–363: 43–46.
- 43 Chou AHK, LeGeros RZ. Development of calcium phosphate mineralized silk for potential use in guided bone regeneration: Preparation and properties. Key Eng Mater 2009; 396–398: 653–657.
- 44 Nakada H, Sakae T, Teranishi M, Kato T, Watanabe T, Takahashi T, Kawai Y, Legeros RZ. Changes in bone quality of the femoral diaphysis induced by high-level fluorine ingestion in ovariectomized rats. Key Eng Mater 2013; 529/530: 341–344.
- 45 Otsuka M, Oshinbe A, Legeros RZ, Tokudome Y, Ito A, Otsuka K, Higuchi WI. Efficacy of the injectable calcium phosphate ceramics suspensions containing magnesium, zinc and fluoride on the bone mineral deficiency in ovariectomized rats. J Pharma Sci 2008; 97: 421–432.
- 46 Sakae T, Nakada H, Teranishi M, Kato T, Suzuki S, Yanagawa A, Yasuda N, Ochiai S, Kitagawa N, Kawai Y, LeGeros RZ. Comparison between the lateral and medial femur in low-mineral- Diet-fed ovariectomized rats using Raman spectral analysis. Key Eng Mater 2013; 529/530: 337–340.
- 47 Tokudome Y, Otsuka M, Ito A, LeGeros RZ. Long-term therapeutic effect of novel calcium phosphate-based compounds injected in ovariectomized rats. J Biomed Mater Res B Appl Biomater 2009; 90: 229–237.
- 48 Weaver CM. The role of nutrition on optimizing peak bone mass. Asia Pac J Clin Nutr 2008; 17: 135–137.
- 49 Nilsson M, Ohlsson C, Oden A, Mellstrom D, Lorentzon M. Increased physical activity is associated with enhanced development of peak bone mass in men: A 5-year longitudinal study. J Bone Miner Res 2012; 27: 1206–1214.
- 50 Bailey CA, Brooke-Wavell K. Exercise for optimising peak bone mass in women. Proc Nutr Soc 2008; 67: 9–18.
- 51 Bradney M, Pearce G, Naughton G, Sullivan C, Bass S, Beck T, Carlson J, Seeman E. Moderate exercise during growth in prepubertal boys: Changes in bone mass, size, volumetric density, and bone strength: A controlled prospective study. J Bone Miner Res 1998; 13: 1814–1821.
- 52 Faulkner RA, Forwood MR, Beck TJ, Mafukidze JC, Russell K, Wallace W. Strength indices of the proximal femur and shaft in prepubertal female gymnasts. Med Sci Sports Exerc 2003; 35: 513–58.
- 53 Moyer-Mileur L, Xie B, Ball S, Bainbridge C, Stadler D, Jee WS. Predictors of bone mass by peripheral quantitative computed tomography in early adolescent girls. J Clin Densitom 2001; 4: 313–323.
- 54 Bonjour JP, Chevalley T, Ferrari S, Rizzoli R. The importance and relevance of peak bone mass in the prevalence of osteoporosis. Salud Publica Mex 2009; 51: S5–S17.
- 55 Mary Bath-Balogh MJF. Illustrated Dental Embryology, Histology, and Anatomy. St. Lois, Missouri: Elsevier Saunders; 2011.
- 56 Li XJJW, Ke HZ, Mori S. Akamine age related changes of cancellous and cortical bone histomorphometry in female Sprague–Dawley rats. Cells Mater Suppl 1992; 1: 25–37.
- 57 Schapira DL-MR, Barzilai D, Silbermann M. The rat as a model for studies of the aging skeleton. Cells Mater Suppl 1992; 1: 181–188.
- 58 Yamaguchi M, Inamoto K, Suketa Y. Effect of essential trace metals on bone metabolism in weanling rats: Comparison with zinc and other metals' actions. Res Exp Med (Berl) 1986; 186: 337–342.
- 59 Yamada Y, Ito A, Kojima H, Sakane M, Miyakawa S, Uemura T, LeGeros RZ. Inhibitory effect of Zn2+ in zinc-containing beta-tricalcium phosphate on resorbing activity of mature osteoclasts. J Biomed Mater Res A 2008; 84: 344–352.
- 60 Sader MS, Legeros RZ, Soares GA. Human osteoblasts adhesion and proliferation on magnesium-substituted tricalcium phosphate dense tablets. J Mater Sci Mater Med 2009; 20: 521–527.
- 61 Fawell J, Bailey K, Chilton J, Dahi E, Fewtrell L, Magara Y. Fluoride in Drinking-water. World Health Organization (WHO). 2006; ISBN: 1900222965. Published by IWA Publishing, London, UK.
- 62 Zhao Y, Ye D. Measurement of biting force of normal teeth at different ages. Hua Xi Yi Ke Da Xue Xue Bao 1994; 25: 414–417.
- 63 Wright NC, Looker AC, Saag KG, Curtis JR, Delzell ES, Randall S, Dawson-Hughes B. The recent prevalence of osteoporosis and low bone mass in the United States based on bone mineral density at the femoral neck or lumbar spine. J Bone Miner Res 2014; 29: 2520–2526.
- 64 Nakada H, Suzuki S, Sakae T, Tanimoto Y, Kuboyama N, Teranishi M, Kato T, Watanabe T, Kimura-Suda H, le Geros RZ, Kawai Y. Quantitative and qualitative analyses of low-mineral-diet ovariectomised rat femora using microscopic computed tomography. J Hard Tissue Biol 2011; 20: 107–114.
- 65 Stoch SA, Wagner JA. Cathepsin K inhibitors: A novel target for osteoporosis therapy. Clin Pharmacol Ther 2008; 83: 172–176.
- 66 Taketa T, Sakai A, Tanaka S, Nakai K, Menuki K, Yamane H, Tanaka K, Nakamura T. Selective cyclooxygenase-2 inhibitor prevents reduction of trabecular bone mass in collagen-induced arthritic mice in association with suppression of RANKL/OPG ratio and IL-6 mRNA expression in synovial tissues but not in bone marrow cells. J Bone Miner Metab 2008; 26: 143–151.
- 67 Liu CC, Hu S, Chen G, Georgiou J, Arns S, Kumar NS, Young RN, Grynpas MD. Novel EP4 receptor agonist-bisphosphonate conjugate drug (C1) promotes bone formation and improves vertebral mechanical properties in the ovariectomized rat model of postmenopausal bone loss. J Bone Miner Res 2015; 30: 670–680.
- 68 Houari S, Wurtz T, Ferbus D, Chateau D, Dessombz A, Berdal A, Babajko S. Asporin and the mineralization process in fluoride-treated rats. J Bone Miner Res 2014; 29: 1446–1455.