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Teriparatide Therapy Reduces Serum Phosphate and Intima-Media Thickness at the Carotid Wall Artery in Patients with Osteoporosis

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Abstract

Although cross-sectional and longitudinal studies report a relationship between osteoporosis and cardiovascular disorders (known as the bone-cardiovascular axis), the benefits of osteoporosis treatment on atherosclerosis are largely unclear. Teriparatide is a bone-forming agent that increases urinary phosphate excretion. Because elevated serum phosphate is associated with the development of atherosclerosis, the purpose of our study was to examine the relationship among lumbar spine bone mineral density (LS-BMD), intima-media thickness at the carotid artery (CA-IMT), and phosphate metabolism in response to daily teriparatide therapy. Osteoporotic patients (n = 28) with low LS-BMD (T-score < −2.5) and/or at least one vertebral fracture were treated with teriparatide (20 μg/day) for 12 months. Metabolic bone markers, LS-BMD, and CA-IMT were measured over the course of treatment. The LS-BMD significantly increased by 0.046 ± 0.038 g/cm2 over the 12-month period (P < 0.001). CA-IMT decreased from 0.701 mm (interquartile range: 0.655–0.774 mm) at baseline to 0.525 mm (0.477–0.670 mm) at 12 months (P < 0.05); however, CA-IMT change was not significantly associated with LS-BMD change. Serum phosphate decreased after 1 month of teriparatide administration, and the change in serum phosphate at 1 months was associated with the change in CA-IMT at 12 months (ρ = 0.431, P = 0.025). Teriparatide improved LS-BMD and CA-IMT, suggesting the existence of the bone–cardiovascular axis. The association between serum phosphate and CA-IMT suggests that the teriparatide decreased CA-IMT in part by reducing serum phosphate, a well-known vascular toxin, in addition to the improvement of bone–cardiovascular axis.

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References

  1. McClung MR, San Martin J, Miller PD, Civitelli R, Bandeira F, Omizo M, Donley DW, Dalsky GP, Eriksen EF (2005) Opposite bone remodeling effects of teriparatide and alendronate in increasing bone mass. Arch Intern Med 165:1762–1768

    Article  CAS  PubMed  Google Scholar 

  2. Tsujimoto M, Chen P, Miyauchi A, Sowa H, Krege JH (2011) PINP as an aid for monitoring patients treated with teriparatide. Bone 48:798–803

    Article  CAS  PubMed  Google Scholar 

  3. Collins TC, Ewing SK, Diem SJ, Taylor BC, Orwoll ES, Cummings SR, Strotmeyer ES, Ensrud KE, Osteoporotic Fractures in Men Study G (2009) Peripheral arterial disease is associated with higher rates of hip bone loss and increased fracture risk in older men. Circulation 119:2305–2312

    Article  Google Scholar 

  4. Schulz E, Arfai K, Liu X, Sayre J, Gilsanz V (2004) Aortic calcification and the risk of osteoporosis and fractures. J Clin Endocrinol Metab 89:4246–4253

    Article  CAS  PubMed  Google Scholar 

  5. Tanko LB, Christiansen C, Cox DA, Geiger MJ, McNabb MA, Cummings SR (2005) Relationship between osteoporosis and cardiovascular disease in postmenopausal women. J Bone Miner Res 20:1912–1920

    Article  PubMed  Google Scholar 

  6. Naves M, Rodriguez-Garcia M, Diaz-Lopez JB, Gomez-Alonso C, Cannata-Andia JB (2008) Progression of vascular calcifications is associated with greater bone loss and increased bone fractures. Osteoporos Int 19:1161–1166

    Article  CAS  PubMed  Google Scholar 

  7. Guerin AP, London GM, Marchais SJ, Metivier F (2000) Arterial stiffening and vascular calcifications in end-stage renal disease. Nephrol Dial Transpl 15:1014–1021

    Article  CAS  Google Scholar 

  8. London GM, Marchais SJ, Guerin AP, Boutouyrie P, Metivier F, de Vernejoul MC (2008) Association of bone activity, calcium load, aortic stiffness, and calcifications in ESRD. J Am Soc Nephrol 19:1827–1835

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Toussaint ND, Lau KK, Strauss BJ, Polkinghorne KR, Kerr PG (2008) Associations between vascular calcification, arterial stiffness and bone mineral density in chronic kidney disease. Nephrol Dial Transplant 23:586–593

    Article  PubMed  Google Scholar 

  10. Bots ML, Hoes AW, Koudstaal PJ, Hofman A, Grobbee DE (1997) Common carotid intima-media thickness and risk of stroke and myocardial infarction: the Rotterdam study. Circulation 96:1432–1437

    Article  CAS  PubMed  Google Scholar 

  11. Okamoto K, Inaba M, Furumitsu Y, Ban A, Mori N, Yukioka K, Imanishi Y, Nishizawa Y (2010) Beneficial effect of risedronate on arterial thickening and stiffening with a reciprocal relationship to its effect on bone mass in female osteoporosis patients: a longitudinal study. Life Sci 87:686–691

    Article  CAS  PubMed  Google Scholar 

  12. Luckish A, Cernes R, Boaz M, Gavish D, Matas Z, Fux A, Shargorodsky M (2008) Effect of long-term treatment with risedronate on arterial compliance in osteoporotic patients with cardiovascular risk factors. Bone 43:279–283

    Article  CAS  PubMed  Google Scholar 

  13. Kang JH, Keller JJ, Lin HC (2013) Bisphosphonates reduced the risk of acute myocardial infarction: a 2-year follow-up study. Osteoporos Int 24:271–277

    Article  CAS  PubMed  Google Scholar 

  14. Toussaint ND, Pedagogos E, Tan SJ, Badve SV, Hawley CM, Perkovic V, Elder GJ (2012) Phosphate in early chronic kidney disease: associations with clinical outcomes and a target to reduce cardiovascular risk. Nephrology (Carlton) 17:433–444

    Article  CAS  Google Scholar 

  15. Dhingra R, Sullivan LM, Fox CS, Wang TJ, D’Agostino RB Sr, Gaziano JM, Vasan RS (2007) Relations of serum phosphorus and calcium levels to the incidence of cardiovascular disease in the community. Arch Intern Med 167:879–885

    Article  CAS  PubMed  Google Scholar 

  16. Ishimura E, Taniwaki H, Tabata T, Tsujimoto Y, Jono S, Emoto M, Shoji T, Inaba M, Inoue T, Nishizawa Y (2005) Cross-sectional association of serum phosphate with carotid intima-medial thickness in hemodialysis patients. Am J Kidney Dis 45:859–865

    Article  CAS  PubMed  Google Scholar 

  17. Ellam T, Wilkie M, Chamberlain J, Crossman D, Eastell R, Francis S, Chico TJ (2011) Dietary phosphate modulates atherogenesis and insulin resistance in apolipoprotein E knockout mice–brief report. Arterioscler Thromb Vasc Biol 31:1988–1990

    Article  CAS  PubMed  Google Scholar 

  18. Six I, Maizel J, Barreto FC, Rangrez AY, Dupont S, Slama M, Tribouilloy C, Choukroun G, Maziere JC, Bode-Boeger S, Kielstein JT, Drueke TB, Massy ZA (2012) Effects of phosphate on vascular function under normal conditions and influence of the uraemic state. Cardiovasc Res 96:130–139

    Article  CAS  PubMed  Google Scholar 

  19. Genant HK, Jergas M, Palermo L, Nevitt M, Valentin RS, Black D, Cummings SR (1996) Comparison of semiquantitative visual and quantitative morphometric assessment of prevalent and incident vertebral fractures in osteoporosis the study of osteoporotic fractures research group. J Bone Miner Res 11:984–996

    Article  CAS  PubMed  Google Scholar 

  20. Yamazaki Y, Emoto M, Morioka T, Kawano N, Lee E, Urata H, Tsuchikura S, Motoyama K, Mori K, Fukumoto S, Shoji T, Nishizawa Y, Inaba M (2013) Clinical impact of the leptin to soluble leptin receptor ratio on subclinical carotid atherosclerosis in patients with type 2 diabetes. J Atheroscler Thromb 20:186–194

    Article  CAS  PubMed  Google Scholar 

  21. Brodehl J, Krause A, Hoyer PF (1988) Assessment of maximal tubular phosphate reabsorption: comparison of direct measurement with the nomogram of Bijvoet. Pediatr Nephrol 2:183–189

    Article  CAS  PubMed  Google Scholar 

  22. Imai E, Horio M, Nitta K, Yamagata K, Iseki K, Tsukamoto Y, Ito S, Makino H, Hishida A, Matsuo S (2007) Modification of the modification of diet in renal disease (MDRD) study equation for Japan. Am J Kidney Dis 50:927–937

    Article  PubMed  Google Scholar 

  23. Gao P, Scheibel S, D’Amour P, John MR, Rao SD, Schmidt-Gayk H, Cantor TL (2001) Development of a novel immunoradiometric assay exclusively for biologically active whole parathyroid hormone 1–84: implications for improvement of accurate assessment of parathyroid function. J Bone Miner Res 16:605–614

    Article  CAS  PubMed  Google Scholar 

  24. Tahtela R, Turpeinen M, Sorva R, Karonen SL (1997) The aminoterminal propeptide of type I procollagen: evaluation of a commercial radioimmunoassay kit and values in healthy subjects. Clin Biochem 30:35–40

    Article  CAS  PubMed  Google Scholar 

  25. Yamazaki Y, Okazaki R, Shibata M, Hasegawa Y, Satoh K, Tajima T, Takeuchi Y, Fujita T, Nakahara K, Yamashita T, Fukumoto S (2002) Increased circulatory level of biologically active full-length FGF-23 in patients with hypophosphatemic rickets/osteomalacia. J Clin Endocrinol Metab 87:4957–4960

    Article  CAS  PubMed  Google Scholar 

  26. Roche B, Vanden-Bossche A, Malaval L, Normand M, Jannot M, Chaux R, Vico L, Lafage-Proust MH (2014) Parathyroid hormone 1–84 targets bone vascular structure and perfusion in mice: impacts of its administration regimen and of ovariectomy. J Bone Miner Res 29:1608–1618

    Article  CAS  PubMed  Google Scholar 

  27. Prisby R, Guignandon A, Vanden-Bossche A, Mac-Way F, Linossier MT, Thomas M, Laroche N, Malaval L, Langer M, Peter ZA, Peyrin F, Vico L, Lafage-Proust MH (2011) Intermittent PTH(1–84) is osteoanabolic but not osteoangiogenic and relocates bone marrow blood vessels closer to bone-forming sites. J Bone Miner Res 26:2583–2596

    Article  CAS  PubMed  Google Scholar 

  28. Kusumbe AP, Ramasamy SK, Adams RH (2014) Coupling of angiogenesis and osteogenesis by a specific vessel subtype in bone. Nature 507:323–328

    Article  CAS  PubMed  Google Scholar 

  29. Ramasamy SK, Kusumbe AP, Wang L, Adams RH (2014) Endothelial Notch activity promotes angiogenesis and osteogenesis in bone. Nature 507:376–380

    Article  CAS  PubMed  Google Scholar 

  30. Hagstrom E, Ahlstrom T, Arnlov J, Larsson A, Melhus H, Hellman P, Lind L (2015) Parathyroid hormone and calcium are independently associated with subclinical vascular disease in a community-based cohort. Atherosclerosis 238:420–426

    Article  PubMed  Google Scholar 

  31. Shao JS, Cheng SL, Charlton-Kachigian N, Loewy AP, Towler DA (2003) Teriparatide (human parathyroid hormone (1–34)) inhibits osteogenic vascular calcification in diabetic low density lipoprotein receptor-deficient mice. J Biol Chem 278:50195–50202

    Article  CAS  PubMed  Google Scholar 

  32. Dobnig H, Turner RT (1997) The effects of programmed administration of human parathyroid hormone fragment (1–34) on bone histomorphometry and serum chemistry in rats. Endocrinology 138:4607–4612

    CAS  PubMed  Google Scholar 

  33. Horwitz MJ, Tedesco MB, Sereika SM, Hollis BW, Garcia-Ocana A, Stewart AF (2003) Direct comparison of sustained infusion of human parathyroid hormone-related protein-(1–36) [hPTHrP-(1–36)] versus hPTH-(1–34) on serum calcium, plasma 1,25-dihydroxyvitamin D concentrations, and fractional calcium excretion in healthy human volunteers. J Clin Endocrinol Metab 88:1603–1609

    Article  CAS  PubMed  Google Scholar 

  34. Deal C, Omizo M, Schwartz EN, Eriksen EF, Cantor P, Wang J, Glass EV, Myers SL, Krege JH (2005) Combination teriparatide and raloxifene therapy for postmenopausal osteoporosis: results from a 6-month double-blind placebo-controlled trial. J Bone Miner Res 20:1905–1911

    Article  CAS  PubMed  Google Scholar 

  35. Anastasilakis AD, Polyzos SA, Goulis DG, Slavakis A, Efstathiadou Z, Kita M, Koukoulis G, Avramidis A (2008) Endogenous intact PTH is suppressed during Teriparatide (rhPTH 1–34) administration in postmenopausal women with established osteoporosis. Endocr J 55:613–616

    Article  CAS  PubMed  Google Scholar 

  36. Kobayashi K, Imanishi Y, Miyauchi A, Onoda N, Kawata T, Tahara H, Goto H, Miki T, Ishimura E, Sugimoto T, Ishikawa T, Inaba M, Nishizawa Y (2006) Regulation of plasma fibroblast growth factor 23 by calcium in primary hyperparathyroidism. Eur J Endocrinol 154:93–99

    Article  CAS  PubMed  Google Scholar 

  37. Kawata T, Imanishi Y, Kobayashi K, Miki T, Arnold A, Inaba M, Nishizawa Y (2007) Parathyroid hormone regulates fibroblast growth factor-23 in a mouse model of primary hyperparathyroidism. J Am Soc Nephrol 18:2683–2688

    Article  CAS  PubMed  Google Scholar 

  38. Sridharan M, Cheung J, Moore AE, Frost ML, Fraser WD, Fogelman I, Hampson G (2010) Circulating fibroblast growth factor-23 increases following intermittent parathyroid hormone (1–34) in postmenopausal osteoporosis: association with biomarker of bone formation. Calcif Tissue Int 87:398–405

    Article  CAS  PubMed  Google Scholar 

  39. Chertow GM, Burke SK, Raggi P, Treat to Goal Working G (2002) Sevelamer attenuates the progression of coronary and aortic calcification in hemodialysis patients. Kidney Int 62:245–252

    Article  CAS  PubMed  Google Scholar 

  40. Block GA, Spiegel DM, Ehrlich J, Mehta R, Lindbergh J, Dreisbach A, Raggi P (2005) Effects of sevelamer and calcium on coronary artery calcification in patients new to hemodialysis. Kidney Int 68:1815–1824

    Article  CAS  PubMed  Google Scholar 

  41. Russo D, Miranda I, Ruocco C, Battaglia Y, Buonanno E, Manzi S, Russo L, Scafarto A, Andreucci VE (2007) The progression of coronary artery calcification in predialysis patients on calcium carbonate or sevelamer. Kidney Int 72:1255–1261

    Article  CAS  PubMed  Google Scholar 

  42. Toussaint ND, Lau KK, Polkinghorne KR, Kerr PG (2011) Attenuation of aortic calcification with lanthanum carbonate versus calcium-based phosphate binders in haemodialysis: a pilot randomized controlled trial. Nephrology (Carlton) 16:290–298

    Article  CAS  Google Scholar 

  43. Suki WN, Zabaneh R, Cangiano JL, Reed J, Fischer D, Garrett L, Ling BN, Chasan-Taber S, Dillon MA, Blair AT, Burke SK (2007) Effects of sevelamer and calcium-based phosphate binders on mortality in hemodialysis patients. Kidney Int 72:1130–1137

    Article  CAS  PubMed  Google Scholar 

  44. Onufrak SJ, Bellasi A, Shaw LJ, Herzog CA, Cardarelli F, Wilson PW, Vaccarino V, Raggi P (2008) Phosphorus levels are associated with subclinical atherosclerosis in the general population. Atherosclerosis 199:424–431

    Article  CAS  PubMed  Google Scholar 

  45. O’Leary DH, Polak JF, Wolfson SK Jr, Bond MG, Bommer W, Sheth S, Psaty BM, Sharrett AR, Manolio TA (1991) Use of sonography to evaluate carotid atherosclerosis in the elderly. The cardiovascular health study. CHS Collaborative Research Group. Stroke 22:1155–1163

    Google Scholar 

  46. Jono S, McKee MD, Murry CE, Shioi A, Nishizawa Y, Mori K, Morii H, Giachelli CM (2000) Phosphate regulation of vascular smooth muscle cell calcification. Circ Res 87:E10–E17

    Article  CAS  PubMed  Google Scholar 

  47. Tonelli M, Sacks F, Pfeffer M, Gao Z, Curhan G, Cholesterol Recurrent Events, Trial I (2005) Relation between serum phosphate level and cardiovascular event rate in people with coronary disease. Circulation 112:2627–2633

    Article  CAS  PubMed  Google Scholar 

  48. Leonard O, Spaak J, Goldsmith D (2013) Regression of vascular calcification in chronic kidney disease—feasible or fantasy? A review of the clinical evidence. Br J Clin Pharmacol 76:560–572

    CAS  PubMed Central  PubMed  Google Scholar 

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Acknowledgments

Maki Yoda contributed to the acquisition, analysis, and interpretation of the data. Yasuo Imanishi and Masaaki Inaba contributed to the conception and design of the study. Yuki Nagata, Masaya Ohara, Koichiro Yoda, Shinsuke Yamada, and Katsuhito Mori contributed to the acquisition of data. Maki Yoda and Koichiro Yoda take responsibility for the integrity of the data analysis. All authors participated in drafting or revising the manuscript and approved the final version of the manuscript for submission.

Conflict of interest

Masaaki Inaba reports grant support and lecture fees from Eli Lilly Japan K.K. Yasuo Imanishi and Katsuhito Mori report lecture fees from Eli Lilly Japan K.K. Maki Yoda, Yuki Nagata, Masaya Ohara, Koichiro Yoda, and Shinsuke Yamada have no conflicts of interest.

Human and Animal Rights and Informed Consent

All participants provided written informed consent before participating in this study, which received institutional ethics committee approval (Osaka City University Graduate School of Medicine, registration number 1775) and was conducted in accordance with the principles of the Declaration of Helsinki.

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  1. Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan

    Maki Yoda, Yasuo Imanishi, Yuki Nagata, Masaya Ohara, Koichiro Yoda, Shinsuke Yamada, Katsuhito Mori & Masaaki Inaba

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  1. Maki Yoda
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Correspondence to Yasuo Imanishi.

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Yoda, M., Imanishi, Y., Nagata, Y. et al. Teriparatide Therapy Reduces Serum Phosphate and Intima-Media Thickness at the Carotid Wall Artery in Patients with Osteoporosis. Calcif Tissue Int 97, 32–39 (2015). https://doi.org/10.1007/s00223-015-0007-4

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