Top

Published in:

01-05-2019 | Original Article

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

Authors: Naohisa Miyakoshi, Masashi Fujii, Yuji Kasukawa, Yoichi Shimada

Published in: Journal of Bone and Mineral Metabolism | Issue 3/2019

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.

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

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 22:1147–1154CrossRefPubMed

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

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

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

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

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

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

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 30:1945–1955CrossRefPubMed

10.

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

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 96:191–198CrossRefPubMed

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 39:171–174CrossRefPubMed

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 58:225–228CrossRefPubMed

14.

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

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 2:30–37CrossRefPubMedPubMedCentral

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 115:1630–1640CrossRefPubMed

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

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 68:255–261CrossRefPubMed

20.

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

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 27:324–332CrossRefPubMed

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 32:259–269CrossRefPubMed

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 33:108–114CrossRefPubMed

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 16:541–549CrossRefPubMed

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 89:402–407CrossRef

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 25:17002CrossRef

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 25:311–319CrossRefPubMed

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 22:457–464CrossRefPubMed

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 51:920–928CrossRefPubMed

30.

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

31.

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

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 63:183–189CrossRefPubMed

33.

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

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 14:418–428CrossRefPubMed

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 20:1853–1861CrossRefPubMed

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 102:1416–1424CrossRefPubMed

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 87:469–484CrossRefPubMed

38.

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

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 47:493–502CrossRefPubMed

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 97:3097–3106CrossRefPubMed

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 344:1434–1441CrossRefPubMed

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 25:921–928CrossRefPubMed

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 19:244–250CrossRefPubMed

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 25:2709–2719CrossRefPubMed

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 43:238–248CrossRefPubMed

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 18:769–775CrossRefPubMed

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 90:4644–4649CrossRefPubMed

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 57:477–483CrossRefPubMed

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 81:247–254CrossRefPubMed

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 49:1160–1165CrossRefPubMed

Title: Impact of vitamin C on teriparatide treatment in the improvement of bone mineral density, strength, and quality in vitamin C-deficient rats
Authors: Naohisa Miyakoshi
Masashi Fujii
Yuji Kasukawa
Yoichi Shimada
Publication date: 01-05-2019
Publisher: Springer Japan
Published in: Journal of Bone and Mineral Metabolism / Issue 3/2019
Print ISSN: 0914-8779
Electronic ISSN: 1435-5604
DOI: https://doi.org/10.1007/s00774-018-0941-0

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

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

Abstract

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3/2019

Bone marrow lesion is associated with disability for activities of daily living in patients with early stage knee osteoarthritis

Study design of multi-center, open-label randomized controlled, head-to-head trial comparing minodronic acid and raloxifene: Japanese Osteoporosis Intervention Trial (JOINT)-04

The relationships between bone variables and physical fitness across the BMI spectrum in young adult women

Finite-element analysis of the mouse proximal ulna in response to elbow loading

Osteoporosis and vertebral fracture are associated with deterioration of activities of daily living and quality of life in patients with type 2 diabetes mellitus

Development of scoliosis in young children with osteogenesis imperfecta undergoing intravenous bisphosphonate therapy

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page