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Impact of vitamin C on teriparatide treatment in the improvement of bone mineral density, strength, and quality in vitamin C-deficient rats

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Abstract

Age-related decreases in serum levels of vitamin C (VC) may negatively affect the efficacy of anti-osteoporotic pharmacotherapy. The purpose of this study was to evaluate the effects of VC and teriparatide (TPTD) on bone mineral density (BMD), strength, and quality in VC-deficient osteogenic disorder Shionogi (ODS) rats. Six-month-old female ODS rats were divided into an untreated ODS control group, a VC group, a TPTD group, and a VC + TPTD group, based on the administration of VC and TPTD (n = 10 each). VC was given as 2.0 mg/ml supplemented water. TPTD was administered subcutaneously once a week at 30 µg/kg body weight. After 12 weeks of treatment, BMDs of the femur and lumbar spine, bone strengths of the femoral diaphysis and metaphysis, and cancellous bone quality of proximal tibiae as estimated by Fourier transform infrared spectroscopy (FTIR) were compared between groups. Compared to the ODS control group, the VC group showed significantly higher total femoral BMD, but the TPTD group showed significantly higher femoral and lumbar spinal BMD, maximum load of femoral metaphysis, and hydroxyapatite (HA) crystallinity by FTIR (p < 0.05). In addition to the increases shown in the TPTD group, the VC + TPTD group also showed significantly higher stiffness of the femoral diaphysis and breaking energy of the femoral metaphysis compared to the ODS control group (p < 0.05). These results indicated that TPTD alone increased cancellous/cortical BMD and cancellous bone strength with improvement of HA crystallinity in ODS rats, but addition of VC supplementation further improved cortical bone strength.

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References

  1. NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy (2001) Osteoporosis prevention, diagnosis, and therapy. JAMA 285:785–795

    Article  Google Scholar 

  2. Nguyen ND, Center JR, Eisman JA, Nguyen TV (2007) Bone loss, weight loss, and weight fluctuation predict mortality risk in elderly men and women. J Bone Miner Res 22:1147–1154

    Article  PubMed  Google Scholar 

  3. Suzuki T, Yoshida H (2010) Low bone mineral density at femoral neck is a predictor of increased mortality in elderly Japanese women. Osteoporos Int 21:71–79

    Article  CAS  PubMed  Google Scholar 

  4. Hernandez CJ, van der Meulen MC (2017) Understanding bone strength is not enough. J Bone Miner Res 32:1157–1162

    Article  PubMed  Google Scholar 

  5. Friedman AW (2006) Important determinants of bone strength: beyond bone mineral density. J Clin Rheumatol 12:70–77

    Article  PubMed  Google Scholar 

  6. Viguet-Carrin S, Garnero P, Delmas PD (2006) The role of collagen in bone strength. Osteoporos Int 17:319–336

    Article  CAS  Google Scholar 

  7. Manolagas SC (2010) From estrogen-centric to aging and oxidative stress: a revised perspective of the pathogenesis of osteoporosis. Endocr Rev 31:266–300

    Article  CAS  PubMed  Google Scholar 

  8. Seeman E, Delmas PD (2006) Bone quality–the material and structural basis of bone strength and fragility. N Engl J Med 354:2250–2261

    Article  CAS  PubMed  Google Scholar 

  9. Aghajanian P, Hall S, Wongworawat MD, Mohan S (2015) The roles and mechanisms of actions of vitamin C in bone: new developments. J Bone Miner Res 30:1945–1955

    Article  CAS  PubMed  Google Scholar 

  10. Nishikimi M (1975) Oxidation of ascorbic acid with superoxide anion generated by the xanthine-xanthine oxidase system. Biochem Biophys Res Commun 63:463–468

    Article  CAS  PubMed  Google Scholar 

  11. Sudo H, Kodama HA, Amagai Y, Yamamoto S, Kasai S (1983) In vitro differentiation and calcification in a new clonal osteogenic cell line derived from newborn mouse calvaria. J Cell Biol 96:191–198

    Article  CAS  PubMed  Google Scholar 

  12. Sugimoto T, Nakada M, Fukase M, Imai Y, Kinoshita Y, Fujita T (1986) Effects of ascorbic acid on alkaline phosphatase activity and hormone responsiveness in the osteoblastic osteosarcoma cell line UMR-106. Calcif Tissue Int 39:171–174

    Article  CAS  PubMed  Google Scholar 

  13. Falch JA, Mowé M, Bøhmer T (1998) Low levels of serum ascorbic acid in elderly patients with hip fracture. Scand J Clin Lab Invest 58:225–228

    Article  CAS  PubMed  Google Scholar 

  14. Richardson TI, Ball L, Rosenfeld T (2002) Will an orange a day keep the doctor away? Postgrad Med J 78:292–294

    Article  CAS  PubMed  Google Scholar 

  15. Segawa T, Miyakoshi N, Kasukawa Y, Aonuma H, Tsuchie H, Shimada Y (2016) Combined treatment with minodronate and vitamin C increases bone mineral density and strength in vitamin C-deficient rats. Osteoporos Sarcopenia 2:30–37

    Article  PubMed  PubMed Central  Google Scholar 

  16. Fujii M, Miyakoshi N, Kasukawa Y, Segawa T, Sato C, Shimada Y (2016) Short term effects of vitamin C and teriparatide on bone mineral density and strength in vitamin C-deficient rats. J Orthop Ther

  17. Horio F, Ozaki K, Yoshida A, Makino S, Hayashi Y (1985) Requirement for ascorbic acid in a rat mutant unable to synthesize ascorbic acid. J Nutr 115:1630–1640

    Article  CAS  PubMed  Google Scholar 

  18. Konishi T, Makino S, Mizushima Y (1990) What is the ODS rat? Historical description of the characterization studies: vitamin C and the scurvy-prone ODS rat. Cancer Lett 49:3–22

    Google Scholar 

  19. Togari A, Arai M, Nakagawa S, Banno A, Aoki M, Matsumoto S (1995) Alteration of bone status with ascorbic acid deficiency in ODS (osteogenic disorder Shionogi) rats. Jpn J Pharmacol 68:255–261

    Article  CAS  PubMed  Google Scholar 

  20. Krane SM, Muñoz AJ, Harris ED Jr (1970) Urinary polypeptides related to collagen synthesis. J Clin Invest 49:716–729

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Hara K, Akiyama Y (2009) Collagen-related abnormalities, reduction in bone quality, and effects of menatetrenone in rats with a congenital ascorbic acid deficiency. J Bone Miner Metab 27:324–332

    Article  CAS  PubMed  Google Scholar 

  22. Hasegawa T, Li M, Hara K, Sasaki M, Tabata C, de Freitas PH, Hongo H, Suzuki R, Kobayashi M, Inoue K, Yamamoto T, Oohata N, Oda K, Akiyama Y, Amizuka N (2011) Morphological assessment of bone mineralization in tibial metaphyses of ascorbic acid-deficient ODS rats. Biomed Res 32:259–269

    Article  CAS  PubMed  Google Scholar 

  23. Suzuki K, Miyakoshi N, Tsuchida T, Kasukawa Y, Sato K, Itoi E (2003) Effects of combined treatment of insulin and human parathyroid hormone(1–34) on cancellous bone mass and structure in streptozotocin-induced diabetic rats. Bone 33:108–114

    Article  CAS  PubMed  Google Scholar 

  24. Tamura Y, Miyakoshi N, Itoi E, Abe T, Kudo T, Tsuchida T, Kasukawa Y, Sato K (2001) Long-term effects of withdrawal of bisphosphonate incadronate disodium (YM175) on bone mineral density, mass, structure, and turnover in the lumbar vertebrae of ovariectomized rats. J Bone Miner Res 16:541–549

    Article  CAS  PubMed  Google Scholar 

  25. Alcantara-Martos T, Delgado-Martinez AD, Vega MV, Carrascal MT, Munuera-Martinez L (2007) Effect of vitamin C on fracture healing in elderly Osteogenic Disorder Shionogi rats. J Bone Jt Surg Br 89:402–407

    Article  CAS  Google Scholar 

  26. Takakura A, Lee JW, Hirano K, Isogai Y, Ishizuya T, Takao-Kawabata R, Iimura T (2017) Administration frequency as well as dosage of PTH are associated with development of cortical porosity in ovariectomized rats. Bone Res 25:17002

    Article  Google Scholar 

  27. Yoshitake K, Yokota K, Kasugai Y, Kagawa M, Sukamoto T, Nakamura T (1999) Effects of 16 weeks of treatment with tibolone on bone mass and bone mechanical and histomorphometric indices in mature ovariectomized rats with established osteopenia on a low-calcium diet. Bone 25:311–319

    Article  CAS  PubMed  Google Scholar 

  28. Kasukawa Y, Miyakoshi N, Itoi E, Tsuchida T, Tamura Y, Kudo T, Suzuki K, Seki A, Sato K (2004) Effects of h-PTH on cancellous bone mass, connectivity, and bone strength in ovariectomized rats with and without sciatic-neurectomy. J Orthop Res 22:457–464

    Article  CAS  PubMed  Google Scholar 

  29. Coleman RM, Aguilera L, Quinones L, Lukashova L, Poirier C, Boskey A (2012) Comparison of bone tissue properties in mouse models with collagenous and non-collagenous genetic mutations using FTIRI. Bone 51:920–928

    Article  CAS  PubMed  Google Scholar 

  30. Murata K, Yano E (2002) Medical statistics for evidence-based medicine with SPBS user’s guide. Nankodo Publisher, Tokyo

    Google Scholar 

  31. Rondanelli M, Opizzi A, Perna S, Faliva MA (2013) Update on nutrients involved in maintaining healthy bone. Endocrinol Nutr 60:197–210

    Article  CAS  PubMed  Google Scholar 

  32. Hall SL, Greendale GA (1998) The relation of dietary vitamin C intake to bone mineral density: results from the PEPI study. Calcif Tissue Int 63:183–189

    Article  CAS  PubMed  Google Scholar 

  33. Morton DJ, Barrett-Connor EL, Schneider DL (2001) Vitamin C supplement use and bone mineral density in postmenopausal women. J Bone Miner Res 16:135–140

    Article  CAS  PubMed  Google Scholar 

  34. Kaptoge S, Welch A, McTaggart A, Mulligan A, Dalzell N, Day NE, Bingham S, Khaw KT, Reeve J (2003) Effects of dietary nutrients and food groups on bone loss from the proximal femur in men and women in the 7th and 8th decades of age. Osteoporos Int 14:418–428

    Article  CAS  PubMed  Google Scholar 

  35. Sahni S, Hannan MT, Gagnon D, Blumberg J, Cupples LA, Kiel DP, Tucker KL (2009) Protective effect of total and supplemental vitamin C intake on the risk of hip fracture–a 17-year follow-up from the Framingham Osteoporosis Study. Osteoporos Int 20:1853–1861

    Article  CAS  PubMed  Google Scholar 

  36. Finck H, Hart AR, Lentjes MA, Jennings A, Luben RN, Khaw KT, Welch AA (2015) Cross-sectional and prospective associations between dietary and plasma vitamin C, heel bone ultrasound, and fracture risk in men and women in the European Prospective Investigation into Cancer in Norfolk cohort. Am J Clin Nutr 102:1416–1424

    Article  CAS  PubMed  Google Scholar 

  37. Gallacher SJ, Dixon T (2010) Impact of treatments for postmenopausal osteoporosis (bisphosphonates, parathyroid hormone, strontium ranelate, and denosumab) on bone quality: a systematic review. Calcif Tissue Int 87:469–484

    Article  CAS  PubMed  Google Scholar 

  38. Miyakoshi N (2004) Effects of parathyroid hormone on cancellous bone mass and structure in osteoporosis. Curr Pharm Des 10:2615–2627

    Article  CAS  PubMed  Google Scholar 

  39. Miyauchi A, Matsumoto T, Sugimoto T, Tsujimoto M, Warner MR, Nakamura T (2010) Effects of teriparatide on bone mineral density and bone turnover markers in Japanese subjects with osteoporosis at high risk of fracture in a 24-month clinical study: 12-month, randomized, placebo-controlled, double-blind and 12-month open-label phases. Bone 47:493–502

    Article  CAS  PubMed  Google Scholar 

  40. Nakamura T, Sugimoto T, Nakano T, Kishimoto H, Ito M, Fukunaga M, Hagino H, Sone T, Yoshikawa H, Nishizawa Y, Fujita T, Shiraki M (2012) Randomized Teriparatide [human parathyroid hormone (PTH) 1–34] Once-Weekly Efficacy Research (TOWER) trial for examining the reduction in new vertebral fractures in subjects with primary osteoporosis and high fracture risk. J Clin Endocrinol Metab 97:3097–3106

    Article  CAS  PubMed  Google Scholar 

  41. Neer RM, Arnaud CD, Zanchetta JR, Prince R, Gaich GA, Reginster JY, Hodsman AB, Eriksen EF, Ish-Shalom S, Genant HK, Wang O, Mitlak BH (2001) Effect of parathyroid hormone (1–34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med 344:1434–1441

    Article  CAS  PubMed  Google Scholar 

  42. Prevrhal S, Krege JH, Chen P, Genant H, Black DM (2009) Teriparatide vertebral fracture risk reduction determined by quantitative and qualitative radiographic assessment. Curr Med Res Opin 25:921–928

    Article  CAS  PubMed  Google Scholar 

  43. Hagino H, Okano T, Akhter MP, Enokida M, Teshima R (2001) Effect of parathyroid hormone on cortical bone response to in vivo external loading of the rat tibia. J Bone Miner Metab 19:244–250

    Article  CAS  PubMed  Google Scholar 

  44. Hofstetter B, Gamsjaeger S, Varga F, Dobnig H, Stepan JJ, Petto H, Pavo I, Klaushofer K, Paschalis EP (2014) Bone quality of the newest bone formed after two years of teriparatide therapy in patients who were previously treatment-naïve or on long-term alendronate therapy. Osteoporos Int 25:2709–2719

    Article  CAS  PubMed  Google Scholar 

  45. Sugiyama T, Saxon LK, Zaman G, Moustafa A, Sunters A, Price JS, Lanyon LE (2008) Mechanical loading enhances the anabolic effects of intermittent parathyroid hormone (1–34) on trabecular and cortical bone in mice. Bone 43:238–248

    Article  CAS  PubMed  Google Scholar 

  46. Paschalis EP, Burr DB, Mendelsohn R, Hock JM, Boskey AL (2003) Bone mineral and collagen quality in humeri of ovariectomized cynomolgus monkeys given rhPTH(1–34) for 18 months. J Bone Miner Res 18:769–775

    Article  CAS  PubMed  Google Scholar 

  47. Paschalis EP, Glass EV, Donley DW, Eriksen EF (2005) Bone mineral and collagen quality in iliac crest biopsies of patients given teriparatide: new results from the fracture prevention trial. J Clin Endocrinol Metab 90:4644–4649

    Article  CAS  PubMed  Google Scholar 

  48. Iwasaki Y, Kazama JJ, Yamato H, Shimoda H, Fukagawa M (2013) Accumulated uremic toxins attenuate bone mechanical properties in rats with chronic kidney disease. Bone 57:477–483

    Article  CAS  PubMed  Google Scholar 

  49. Iwasaki Y, Kazama JJ, Yamato H, Matsugaki A, Nakano T, Fukagawa M (2015) Altered material properties are responsible for bone fragility in rats with chronic kidney injury. Bone 81:247–254

    Article  PubMed  Google Scholar 

  50. Gamsjaeger S, Buchinger B, Zoehrer R, Phipps R, Klaushofer K, Paschalis EP (2011) Effects of one year daily teriparatide treatment on trabecular bone material properties in postmenopausal osteoporotic women previously treated with alendronate or risedronate. Bone 49:1160–1165

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors would like to thank Asahi Kasei Pharma Corporation for providing TPTD and Ms. Ran Matsuzawa for her support of our experiment.

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Correspondence to Naohisa Miyakoshi.

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Miyakoshi, N., Fujii, M., Kasukawa, Y. et al. Impact of vitamin C on teriparatide treatment in the improvement of bone mineral density, strength, and quality in vitamin C-deficient rats. J Bone Miner Metab 37, 411–418 (2019). https://doi.org/10.1007/s00774-018-0941-0

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  • DOI: https://doi.org/10.1007/s00774-018-0941-0

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