Skip to main content

Advertisement

Log in

Improved Trabecular Bone Structure of 20-Month-Old Male Spontaneously Hypertensive Rats

  • Original Research
  • Published:
Calcified Tissue International Aims and scope Submit manuscript

Abstract

A few clinical studies have reported that elderly male participants with hypertensive disease frequently have higher bone mineral density (BMD) than the normotensive participants at several skeletal sites. The detailed mechanism is still unknown; therefore, a study of bone structure and density using the hypertensive animal models could be informative. We used micro-computed tomography to quantitatively evaluate the tibial and 3rd lumbar vertebral bones in the 20-month-old male spontaneous hypertensive rat (SHR). The BMD, volume fraction, and the microarchitecture changes of the SHR were compared to those of same-age normotensive controls (Wistar-Kyoto rat, WKY). We found that in the very old (20 month) male rats, the trabecular bone fraction and microstructure were higher than those in the same-age normotensive controls. The observation of the association of hypertension with BMD and bone strength in hypertensive rats warrants further investigations of bone mass and strength in elderly males with hypertension.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Cappuccio FP, Kalaitzidis R, Duneclift S, Eastwood JB (2000) Unravelling the links between calcium excretion, salt intake, hypertension, kidney stones and bone metabolism. J Nephrol 13:169–177

    CAS  PubMed  Google Scholar 

  2. Cappuccio FP, Meilahn E, Zmuda JM, Cauley JA (1999) High blood pressure and bone-mineral loss in elderly white women: a prospective study. The Lancet 354:971–975

    Article  CAS  Google Scholar 

  3. Vestergaard P, Rejnmark L, Mosekilde L (2009) Hypertension is a risk factor for fractures. Calcif Tissue Int 84:103–111

    Article  CAS  PubMed  Google Scholar 

  4. Butt DA, Mamdani M, Austin PC, Tu K, Gomes T, Glazier RH (2012) The risk of hip fracture after initiating antihypertensive drugs in the elderly. Arch Intern Med 172:1739–1744

    Article  PubMed  Google Scholar 

  5. Schlienger RG, Kraenzlin ME, Jick SS, Meier CR (2004) Use of β-blockers and risk of fractures. JAMA 292:1326–1332

    Article  CAS  PubMed  Google Scholar 

  6. Rejnmark L, Vestergaard P, Mosekilde L (2006) Treatment with beta-blockers, ACE inhibitors, and calcium-channel blockers is associated with a reduced fracture risk: a nationwide case–control study. J Hypertens 24:581–589

    Article  CAS  PubMed  Google Scholar 

  7. Wright GL, DeMoss D (2000) Evidence for dramatically increased bone turnover in spontaneously hypertensive rats. Metabolism 49:1130–1133

    Article  CAS  PubMed  Google Scholar 

  8. Wang T-M, Hsu J-F, Jee WSS, Matthews JL (1993) Evidence for reduced cancellous bone mass in the spontaneously hypertensive rat. Bone Miner 20:251–264

    Article  CAS  PubMed  Google Scholar 

  9. Merke J, Lucas P, Szabo A, Cournot-Witmer G, Mall G, Bouillon R, Drueke T, Mann J, Ritz E (1989) Hyperparathyroidism and abnormal calcitriol metabolism in the spontaneously hypertensive rat. Hypertension 13:233–242

    Article  CAS  PubMed  Google Scholar 

  10. Izawa Y, Sagara K, Kadota T, Makita T (1985) Bone disorders in spontaneously hypertensive rat. Calcif Tissue Int 37:605–607

    Article  CAS  PubMed  Google Scholar 

  11. Sato T, Arai M, Goto S, Togari A (2010) Effects of propranolol on bone metabolism in spontaneously hypertensive rats. J Pharmacol Exp Ther 334:99–105

    Article  CAS  PubMed  Google Scholar 

  12. Lalande A, Roux C, Graulet A-M, Schiavi P, De Vernejoul M-C (1998) The diuretic indapamide increases bone mass and decreases bone resorption in spontaneously hypertensive rats supplemented with sodium. J Bone Miner Res 13:1444–1450

    Article  CAS  PubMed  Google Scholar 

  13. Shimizu H, Nakagami H, Osako MK, Nakagami F, Kunugiza Y, Tomita T, Yoshikawa H, Rakugi H, Ogihara T, Morishita R (2009) Prevention of osteoporosis by angiotensin-converting enzyme inhibitor in spontaneous hypertensive rats. Hypertens Res 32:786–790

    Article  CAS  PubMed  Google Scholar 

  14. Cauley J, Fullman R, Stone K, Zmuda J, Bauer D, Barrett-Connor E, Ensrud K, Lau E, Orwoll E (2005) Group, F.T.M.O.S.R.: Factors associated with the lumbar spine and proximal femur bone mineral density in older men. Osteoporos Int 16:1525–1537

    Article  PubMed  Google Scholar 

  15. Orwoll ES, Bevan L, Phipps KR (2000) Determinants of bone mineral density in older men. Osteoporos Int 11:815–821

    Article  CAS  PubMed  Google Scholar 

  16. Barbour KE, Zmuda JM, Strotmeyer ES, Horwitz MJ, Boudreau R, Evans RW, Ensrud KE, Petit MA, Gordon CL, Cauley JA (2010) Osteoporotic Fractures Men Mr, O.S.R.: correlates of trabecular and cortical volumetric bone mineral density of the radius and tibia in older men: the osteoporotic fractures in men study. J Bone Miner Res 25:1017–1028

    Article  PubMed Central  PubMed  Google Scholar 

  17. Liang H, Ma Y, Pun S, Stimpel M, Jee WSS (1997) Aging- and ovariectomy-related skeletal changes in spontaneously hypertensive rats. Anat Rec 249:173–180

    Article  CAS  PubMed  Google Scholar 

  18. Hernandez AM, Huber JS, Murphy ST, Janabi M, Zeng GL, Brennan KM, O’Neil JP, Seo Y, Gullberg GT (2013) Longitudinal evaluation of left ventricular substrate metabolism, perfusion, and dysfunction in the spontaneously hypertensive rat model of hypertrophy using small-animal PET/CT imaging. J Nucl Med 54:1938–1945

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Burghardt A, Kazakia G, Laib A, Majumdar S (2008) Quantitative assessment of bone tissue mineralization with polychromatic micro-computed tomography. Calcif Tissue Int 83:129–138

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Buie HR, Campbell GM, Klinck RJ, MacNeil JA, Boyd SK (2007) Automatic segmentation of cortical and trabecular compartments based on a dual threshold technique for in vivo micro-CT bone analysis. Bone 41:505–515

    Article  PubMed  Google Scholar 

  21. Ridler TW (1978) Picture thresholding using an iterative selection method. IEEE trans syst Man Cybern 8:630–632

    Article  Google Scholar 

  22. Hildebrand T, Laib A, Müller R, Dequeker J, Rüegsegger P (1999) Direct three-dimensional morphometric analysis of human cancellous bone: microstructural data from spine, femur, iliac crest, and calcaneus. J Bone Miner Res 14:1167–1174

    Article  CAS  PubMed  Google Scholar 

  23. Laib A, Hauselmann HJ, Rüegsegger P (1998) In vivo high resolution 3D-QCT of the human forearm. Technol Health Care 6:329

    CAS  PubMed  Google Scholar 

  24. Hildebrand T, Rüegsegger P (1997) A new method for the model-independent assessment of thickness in three-dimensional images. J Microsc 185:67–75

    Article  Google Scholar 

  25. Hildebrand TOR, Rüegsegger P (1997) Quantification of bone microarchitecture with the structure model index. Comput Methods Biomech Biomed Eng 1:15–23

    Article  Google Scholar 

  26. Odgaard A, Gundersen HJ (1993) Quantification of connectivity in cancellous bone, with special emphasis on 3-D reconstructions. Bone 14:173–182

    Article  CAS  PubMed  Google Scholar 

  27. Harrigan TP, Mann RW (1984) Characterization of microstructural anisotropy in orthotropic materials using a second rank tensor. J Mater Sci 19:761–767

    Article  CAS  Google Scholar 

  28. Müller R, Rüegsegger P (1995) Three-dimensional finite element modelling of non-invasively assessed trabecular bone structures. Med Eng Phys 17:126–133

    Article  PubMed  Google Scholar 

  29. Van Rietbergen B, Weinans H, Huiskes R, Odgaard A (1995) A new method to determine trabecular bone elastic properties and loading using micromechanical finite-element models. J Biomech 28:69–81

    Article  PubMed  Google Scholar 

  30. Van Rietbergen B, Odgaard A, Kabel J, Huiskes R (1996) Direct mechanics assessment of elastic symmetries and properties of trabecular bone architecture. J Biomech 29:1653–1657

    Article  PubMed  Google Scholar 

  31. Yao W, Dai W, Shahnazari M, Pham A, Chen Z, Chen H, Guan M, Lane NE (2010) Inhibition of the progesterone nuclear receptor during the bone linear growth phase increases peak bone mass in female mice. PLoS One 5:e11410

    Article  PubMed Central  PubMed  Google Scholar 

  32. Yao W, Cheng Z, Shahnazari M, Dai W, Johnson ML, Lane NE (2010) Overexpression of secreted frizzled-related protein 1 inhibits bone formation and attenuates parathyroid hormone bone anabolic effects. J Bone Miner Res 25:190–199

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Yao W, Cheng Z, Pham A, Busse C, Zimmermann EA, Ritchie RO, Lane NE (2008) Glucocorticoid-induced bone loss in mice can be reversed by the actions of parathyroid hormone and risedronate on different pathways for bone formation and mineralization. Arthritis Rheum 58:3485–3497

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  34. Dempster DW, Compston JE, Drezner MK, Glorieux FH, Kanis JA, Malluche H, Meunier PJ, Ott SM, Recker RR, Parfitt AM (2012) Standardized nomenclature, symbols, and units for bone histomorphometry: a 2012 update of the report of the ASBMR histomorphometry nomenclature committee. J Bone Miner Res 28:2–17

    Article  Google Scholar 

  35. Lane NE, Yao W, Kinney JH, Modin G, Balooch M, Wronski TJ (2003) Both hPTH(1–34) and bFGF increase trabecular bone mass in osteopenic rats but they have different effects on trabecular bone architecture. J Bone Miner Res 18:2105–2115

    Article  CAS  PubMed  Google Scholar 

  36. Offley SC, Guo T-Z, Wei T, Clark JD, Vogel H, Lindsey DP, Jacobs CR, Yao W, Lane NE, Kingery WS (2005) Capsaicin-sensitive sensory neurons contribute to the maintenance of trabecular bone integrity. J Bone Miner Res 20:257–267

    Article  PubMed  Google Scholar 

  37. Mittra E, Rubin C, Qin Y-X (2005) Interrelationship of trabecular mechanical and microstructural properties in sheep trabecular bone. J Biomech 38:1229–1237

    Article  PubMed  Google Scholar 

  38. Guo XE, Kim CH (2002) Mechanical consequence of trabecular bone loss and its treatment: a three-dimensional model simulation. Bone 30:404–411

    Article  CAS  PubMed  Google Scholar 

  39. Lucas PA, Brown RC, Drüeke T, Lacour B, Metz JA, McCarron DA (1986) Abnormal vitamin D metabolism, intestinal calcium transport, and bone calcium status in the spontaneously hypertensive rat compared with its genetic control. J Clin Invest 78:221–227

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  40. Charhon SA, Edouard CM, Arlot ME, Meunier PJ (1982) Effects of parathyroid hormone on remodeling of iliac trabecular bone packets in patients with primary hyperparathyroidism. Clin Orthop Relat Res 162:255–263

    PubMed  Google Scholar 

  41. Crowley SD, Gurley SB, Herrera MJ, Ruiz P, Griffiths R, Kumar AP, Kim H-S, Smithies O, Le TH, Coffman TM (2006) Angiotensin II causes hypertension and cardiac hypertrophy through its receptors in the kidney. Proc Natl Acad Sci U.S.A 103:17985–17990

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  42. Shimizu H, Nakagami H, Osako MK, Hanayama R, Kunugiza Y, Kizawa T, Tomita T, Yoshikawa H, Ogihara T, Morishita R (2008) Angiotensin II accelerates osteoporosis by activating osteoclasts. FASEB J 22:2465–2475

    Article  CAS  PubMed  Google Scholar 

  43. de Champlain J, Wu R, Girouard H, Karas M, EL Midaoui A, Laplante MA, Wu L (2004) Oxidative Stress in Hypertension. Clin Exp Hypertens 26:593–601

    Article  PubMed  Google Scholar 

  44. Sowers JR (2013) Hypertension, angiotensin II, and oxidative stress. N Engl J Med 346:1999–2001

    Article  Google Scholar 

  45. Sánchez-Rodríguez MA, Ruiz-Ramos M, Correa-Muñoz E, Mendoza-Núñez VM (2007) Oxidative stress as a risk factor for osteoporosis in elderly Mexicans as characterized by antioxidant enzymes. BMC Musculoskelet Disord 8:124

    Article  PubMed Central  PubMed  Google Scholar 

  46. Sugiura M, Nakamura M, Ogawa K, Ikoma Y, Ando F, Yano M (2008) Bone mineral density in post-menopausal female subjects is associated with serum antioxidant carotenoids. Osteoporos Int 19:211–219

    Article  CAS  PubMed  Google Scholar 

  47. Sahni S, Hannan MT, Blumberg J, Cupples LA, Kiel DP, Tucker KL (2008) Inverse association of carotenoid intakes with 4-y change in bone mineral density in elderly men and women: the framingham osteoporosis study. Am J Clin Nutr 89:416–424

    Article  PubMed Central  PubMed  Google Scholar 

  48. Nabipour I, Sambrook PN, Blyth FM, Janu MR, Waite LM, Naganathan V, Handelsman DJ, Le Couteur DG, Cumming RG, Seibel MJ (2011) Serum uric acid is associated with bone health in older men: a cross-sectional population-based study. J Bone Miner Res 26:955–964

    Article  CAS  PubMed  Google Scholar 

  49. Makovey J, Macara M, Chen JS, Hayward CS, March L, Seibel MJ, Sambrook PN (2013) Serum uric acid plays a protective role for bone loss in peri- and postmenopausal women: A longitudinal study. Bone 52:400–406

    Article  CAS  PubMed  Google Scholar 

  50. Feig DI (2011) Uric acid and hypertension. Semin Nephrol 31:441–446

    Article  CAS  PubMed  Google Scholar 

  51. Perlstein TS, Gumieniak O, Williams GH, Sparrow D, Vokonas PS, Gaziano M, Weiss ST, Litonjua AA (2006) Uric acid and the development of hypertension: the normative aging study. Hypertension 48:1031–1036

    Article  CAS  PubMed  Google Scholar 

  52. Puig JG, Ruilope LM (1999) Uric acid as a cardiovascular risk factor in arterial hypertension. J Hypertens 17:869–872

    Article  CAS  PubMed  Google Scholar 

  53. Mazzali M, Hughes J, Kim YG, Jefferson JA, Kang DH, Gordon KL, Lan HY, Kivlighn S, Johnson RJ (2001) Elevated uric acid increases blood pressure in the rat by a novel crystal-independent mechanism. Hypertension 38:1101–1106

    Article  CAS  PubMed  Google Scholar 

  54. Trachtman H, Valderrama E, Futterweit S (1991) Nephrotoxicity of allopurinol is enhanced in experimental hypertension. Hypertension 17:194–202

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors would like to thanks Dr. Kathleen Brennan (LBNL) and Ms. Stephanie Murphy (UCSF, Radiology) for handling the serum test and harvesting the bone samples. The study was supported in part by the National Institutes of Health of the U. S. Department of Health and Human Services under grants R01 EB007219 (GTG), R01 AG17762 (SM), and R01 EB012965 (YS), and by the Director, Office of Science, Office of Biological and Environmental Research of the U. S. Department of Energy under contract DE-AC02-05CH11231 (GTG).

Human and Animal Rights and Informed Consent

All in vivo animal studies in this study were performed in accordance with the protocols approved by Institutional Animal Care and Use Committee (IACUC) from both University of California, San Francisco (UCSF) and Lawrence Berkeley National Laboratory (LBNL).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Youngho Seo.

Additional information

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lee, TC., Burghardt, A.J., Yao, W. et al. Improved Trabecular Bone Structure of 20-Month-Old Male Spontaneously Hypertensive Rats. Calcif Tissue Int 95, 282–291 (2014). https://doi.org/10.1007/s00223-014-9893-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00223-014-9893-0

Keywords

Navigation