Skip to main content
SpringerLink
Log in

Bone mineral density in statin users: a population-based analysis from a Spanish cohort

  • Original Article
  • Published:
Journal of Bone and Mineral Metabolism Aims and scope Submit manuscript

Abstract

We studied 2,315 subjects (1,422 women and 893 men) from the Camargo Cohort and analyzed the differences in BMD between statin or non-statin users. We also studied effects of the type of statin, dose, pharmacokinetic properties, and length of treatment on bone mineral density (BMD). Of the subjects, 478 (21 %) were taking statins (256 women and 222 men). Overall, they had higher BMD than non-users (p < 0.0001). In adjusted multivariate models, women taking statins had higher BMD at femoral neck (p = 0.002) and total hip (p = 0.04) than non- users. No differences were found in men. Women taking simvastatin had higher increases in BMD than non-statin users at femoral neck (p = 0.02) and total hip (p = 0.009), those taking fluvastatin had lower BMD values at lumbar spine (p = 0.028), and those receiving lovastatin had higher increases at femoral neck (p = 0.006). In men, only atorvastatin was associated with higher femoral neck BMD than non-statin use (p = 0.029). Comparing with non-statin users, only women receiving lipophilic statins had greater BMD at femoral neck (p = 0.003). According to drug potency, women on high- or lower-potency agents showed higher BMD values at femoral neck than non-users (p = 0.028 and 0.022, respectively). In men, only high-potency statins were associated with higher femoral neck BMD than non-use (p = 0.021). No differences between dose or length of statin therapy were noted regarding BMD in either sex. In summary, in a large population-based cohort, women on statins had higher BMD at the hip than non-users. Overall, this increase in BMD was more evident in subjects on lipophilic or high-potency statins.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Liao JK, Laufs U (2005) Pleiotropic effects of statins. Annu Rev Pharmacol Toxicol 45:89–118

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  2. Patil S, Holt G, Raby N, McLellan AR, Smith K, O’Kane S, Beastall G, Crossan JF (2009) Prospective, double blind, randomized, controlled trial of simvastatin in human fracture healing. J Orthop Res 27:281–285

    Article  CAS  PubMed  Google Scholar 

  3. Mundy G, Garrett R, Harris S, Chan J, Chen D, Rossini G, Boyce B, Zhao M, Gutiérrez G (1999) Stimulation of bone formation in vitro and in rodents by statins. Science 286:1946–1949

    Article  CAS  PubMed  Google Scholar 

  4. Ohnaka K, Shimoda S, Nawata H, Shimokawa H, Kaibuchi K, Iwamoto Y, Takayanagi R (2001) Pitavastatin enhanced BMP-2 and osteocalcin expression by inhibition of rho-associated kinase in human osteoblasts. Biochem Biophys Res Commun 287:337–342

    Article  CAS  PubMed  Google Scholar 

  5. Woo JT, Kasai S, Stern PH, Nagai K (2000) Compactin suppresses bone resorption by inhibiting the fusion of perfusion osteoclasts and disrupting the actin ring in osteoclasts. J Bone Miner Res 15:650–662

    Article  CAS  PubMed  Google Scholar 

  6. Bauer DC (2003) HMG CoA reductase inhibitors and the skeleton: a comprehensive review. Osteoporos Int 14:273–282

    Article  CAS  PubMed  Google Scholar 

  7. Bauer DC, Mundy GR, Jamal SA, Black DM, Cauley JA, Ensrud KE, van der Klift M, Pols HA (2004) Use of statins and fracture: results of 4 prospective studies and cumulative meta-analysis of observational studies and controlled trials. Arch Intern Med 164:146–152

    Article  CAS  PubMed  Google Scholar 

  8. Hatzigeorgiou C, Jackson JL (2005) Hydroxymethylglutaryl-coenzyme A reductase inhibitors and osteoporosis: a meta-analysis. Osteoporos Int 16:990–996

    Article  CAS  PubMed  Google Scholar 

  9. Uzzan B, Cohen R, Nicolas P, Cucherat M, Perret GY (2007) Effects of statins on bone mineral density: a meta-analysis of clinical studies. Bone (NY) 40:1581–1587

    Article  CAS  Google Scholar 

  10. Yue J, Zhang X, Dong B, Yang M (2010) Statins and bone health in postmenopausal women: a systematic review of randomized controlled trials. Menopause 17:1071–1079

    Article  PubMed  Google Scholar 

  11. Ross I, Mundy G (2002) The role of statins as potential targets for bone formation. Arthritis Res 4:237–240

    Article  Google Scholar 

  12. Chuengsamarn S, Rattanamongkoulgul S, Suwanwalaikorn S, Wattanasirichaigoon S, Kaufman L (2010) Effects of statins vs. non-statin lipid-lowering therapy on bone formation and bone mineral density biomarkers in patients with hyperlipidemia. Bone (NY) 46:1011–1015

    Article  CAS  Google Scholar 

  13. Hernández JL, Olmos JM, Pariente E, Martínez J, Valero C, García-Velasco P, Nan D, Llorca J, González-Macías J (2010) Metabolic syndrome and bone metabolism. Menopause 17:955–961

    Article  PubMed  Google Scholar 

  14. Hernández JL, Olmos JM, Ramos C, Martínez J, de Juan J, Valero C, Nan D, González-Macías J (2010) Serum lipids and bone metabolism in Spanish men: the Camargo Cohort Study. Endocr J 57:51–60

    Article  PubMed  Google Scholar 

  15. Díez A, González-Macías J, Marín F, Abizanda M, Alvarez R, Gimeno A, Pegenaute E, Vila J (2007) Prediction of absolute risk of nonspinal fractures using clinical risk factors and heel quantitative ultrasound. Osteoporos Int 18:629–639

    Article  Google Scholar 

  16. Weng TC, Yang YH, Lin SJ, Tai SH (2010) A systematic review and meta-analysis on the therapeutic equivalence of statins. J Clin Pharmacol Ther 35:139–151

    Article  CAS  Google Scholar 

  17. Alberti KG, Zimmet PZ (1998) Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: Diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabetes Med 15:539–553

    Article  CAS  Google Scholar 

  18. Berry EM, Gupta MM, Turner SJ, Burns RR (1973) Variations in plasma calcium with induced changes in plasma specific gravity, total protein, and albumin. Br Med J 4:640–643

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D (1999) A more accurate method to estimate glomerular filtration rate from serum creatinine, a new prediction equation. Modification of diet in Renal Disease Study Group. Ann Intern Med 130:461–470

    Article  CAS  PubMed  Google Scholar 

  20. Garnero P, Vergnaud P, Hoyle N (2008) Evaluation of a fully automated serum assay for total N-terminal propeptide of type I collagen in postmenopausal osteoporosis. Clin Chem 54:188–196

    Article  CAS  PubMed  Google Scholar 

  21. Olmos JM, Hernández JL, Martínez J, Pariente E, Llorca J, González-Macías J (2010) Bone turnover markers in Spanish adult men. The Camargo Cohort Study. Clin Chim Acta 411:1511–1515

    Article  CAS  PubMed  Google Scholar 

  22. Martínez J, Olmos JM, Hernández JL, Pinedo G, Llorca J, Obregón E, Valero C, González-Macías J (2009) Bone turnover markers in Spanish postmenopausal women. The Camargo Cohort Study. Clin Chim Acta 409:70–74

    Article  PubMed  Google Scholar 

  23. Riancho JA, Valero C, Hernández JL, Olmos JM, Paule B, Zarrabeitia A, González-Macías J (2007) Biomechanical indices of the femoral neck estimated from the standard DXA output, age- and sex-related differences. J Clin Densitom 10:39–45

    Article  PubMed  Google Scholar 

  24. Solomon DH, Avorn J, Canning CF, Wang PS (2005) Lipid levels and bone mineral density. Am J Med 118:1414.e1–1414.e5

    Article  Google Scholar 

  25. Klein S, Allison DB, Heymsfield SB, Kelley DE, Leibel RL, Nonas C, Kahn R, Association for Weight Management and Obesity Prevention; NAASO, The Obesity Society; American Society for Nutrition; American Diabetes Association (2007) Waist circumference and cardiometabolic risk: a consensus statement from Shaping America’s Health: Association for Weight Management and Obesity Prevention; NAASO, The Obesity Society; the American Society for Nutrition; and the American Diabetes Association. Am J Clin Nutr 85:1197–1202

    CAS  PubMed  Google Scholar 

  26. Fisher JE, Rogers MJ, Halasy JM, Luckman SP, Hughes DE, Masarachia PJ, Wesolowski G, Russell RG, Rodan GA, Reszka AA (1999) Alendronate mechanism of action: geranylgeraniol, an intermediate in the mevalonate pathway, prevents inhibition of osteoclast formation, bone resorption, and kinase activation in vitro. Proc Natl Acad Sci USA 96:133–138

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Montagnani A, Gonelli S, Cepollaro C, Pacini S, Campagna MS, Franci MB, Lucani B, Gennari C (2003) Effect of simvastatin treatment on bone mineral density and bone turnover in hypercholesterolemic postmenopausal women: a 1-year longitudinal study. Bone (NY) 23:427–433

    Article  Google Scholar 

  28. Lupattelli G, Scarponi AM, Vaudo G, Siepi D, Roscini AR, Gemelli F, Pirro M, Latini RA, Sinzinger H, Marchesi S, Mannarino E (2004) Simvastatin increases bone mineral density in hypercholesterolemic postmenopausal women. Metabolism 53:744–748

    Article  CAS  PubMed  Google Scholar 

  29. Rosenson RS, Tangney CC, Langman CB, Parker TS, Levine DM, Gordon BR (2005) Short term reduction in bone markers with high-dose simvastatin. Osteoporos Int 16:1272–1276

    Article  PubMed  Google Scholar 

  30. Rejnmark L, Buus NH, Vestergaard P, Heickendorff L, Andreasen F, Larsen ML, Mosekilde L (2004) Effects of simvastatin on bone turnover and BMD: a 1-year randomized controlled trial in postmenopausal osteopenic women. J Bone Miner Res 19:737–744

    Article  CAS  PubMed  Google Scholar 

  31. Bone HG, Kiel DP, Lindsay RS, Lewiecki EM, Bolognese MA, Leary ET, Lowe W, McClung MR (2007) Effects of atorvastatin on bone in postmenopausal women with dyslipidemia: a double-blind, placebo-controlled, dose-ranging trial. J Clin Endocrinol Metab 92:4671–4677

    Article  CAS  PubMed  Google Scholar 

  32. Bjarnason NH, Riis BJ, Christiansen C (2001) The effect of fluvastatin on parameters of bone remodeling. Osteoporos Int 12:380–384

    Article  CAS  PubMed  Google Scholar 

  33. Williams D, Feely J (2002) Pharmacokinetic-pharmacodynamic drug interactions with HMG-CoA reductase inhibitors. Clin Pharmacokinet 41:343–370

    Article  CAS  PubMed  Google Scholar 

  34. Pérez-Castrillón JL, Abad L, Vega G, Sanz-Cantalapiedra A, García-Porrero M, Pinacho F, Dueñas A (2008) Effect of atorvastatin on bone mineral density in patients with acute coronary syndrome. Eur Rev Med Pharmacol Sci 12:83–88

    PubMed  Google Scholar 

  35. Staal A, Frith JC, French MH, Swartz J, Gungor T, Harrity TW, Tamasi J, Rogers MJ, Feyen JH (2003) The ability of statins to inhibit bone resorption is directly related to their inhibitory effect on HMG-CoA reductase activity. J Bone Miner Res 18:88–96

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Supported by a grant from the “Instituto de Salud Carlos III-FIS”. Spain (PI11/01092).

Conflict of interest

All authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Bone Metabolic Unit, Department of Internal Medicine, Hospital Universitario Marqués de Valdecilla, University of Cantabria, IFIMAV, Red temática de investigación cooperativa en envejecimiento y fragilidad (RETICEF), Cantabria, Spain

    José L. Hernández, José M. Olmos, Josefina Martinez, Irina Yezerska & Jesús González-Macías

  2. Centro de Salud Camargo, Cantabria, Spain

    Galo Romaña, Jesús Castillo & Gabriel Pinedo

Authors
  1. José L. Hernández
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. José M. Olmos
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Galo Romaña
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Josefina Martinez
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jesús Castillo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Irina Yezerska
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Gabriel Pinedo
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jesús González-Macías
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to José L. Hernández.

About this article

Cite this article

Hernández, J.L., Olmos, J.M., Romaña, G. et al. Bone mineral density in statin users: a population-based analysis from a Spanish cohort. J Bone Miner Metab 32, 184–191 (2014). https://doi.org/10.1007/s00774-013-0481-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00774-013-0481-6

Keywords

Search

Navigation