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The effects of low dose parathyroid hormone on lumbar vertebrae in a rat model for chronic alcohol abuse

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Abstract

Summary

This study evaluated the hypothesis that increased bone marrow adipogenesis is coupled to decreased bone formation in rats consuming alcohol. Parathyroid hormone (PTH) increased bone formation but had no effect on marrow adiposity. We conclude that increased adiposity does not prevent the bone anabolic response to PTH.

Introduction

Alcoholism results in decreased bone formation and increased bone marrow adiposity. The present study tested the hypothesis that these reciprocal changes are coupled by evaluating the effect of intermittent PTH on bone formation and bone marrow adiposity in a rat model for chronic alcohol abuse.

Methods

Three-month-old male Sprague Dawley rats (n = 10–11/group) were fed the Lieber-DeCarli liquid diet with 35% of the calories derived from ethanol. Control rats were pair-fed an isocaloric alcohol-free diet. The rats were administered low dose PTH (1 µg/kg/day sc, 5 d/week) or vehicle for 6 weeks. Cancellous bone architecture in lumbar vertebrae was evaluated by micro-computed tomography followed by histomorphometric assessment of bone formation and marrow adiposity.

Results

Alcohol increased bone marrow adiposity but reduced bone formation. The latter was due to decreases in mineralizing perimeter/bone perimeter, a surrogate measure of osteoblast number, and mineral apposition rate, a measure of osteoblast activity. PTH increased bone formation by increasing mineralizing perimeter/bone perimeter. In contrast, PTH had no effect on mineral apposition rate or bone marrow adiposity. Interactions between alcohol consumption and PTH treatment were not detected for any endpoints evaluated.

Conclusions

PTH treatment blunted the decrease in mineralizing perimeter/bone perimeter in alcohol-fed rats but was ineffective in preventing the increase in bone marrow adiposity. These findings suggest that the alcohol-induced increase in adipocytes is not directly responsible for the accompanying reduction in bone formation.

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References

  1. Malik P, Gasser RW, Kemmler G, Moncayo R, Finkenstedt G, Kurz M, Fleischhacker WW (2009) Low bone mineral density and impaired bone metabolism in young alcoholic patients without liver cirrhosis: a cross-sectional study. Alcohol Clin Exp Res 33:375–381

    Article  PubMed  CAS  Google Scholar 

  2. Bikle DD, Stesin A, Halloran B, Steinbach L, Recker R (1993) Alcohol-induced bone disease: relationship to age and parathyroid hormone levels. Alcohol Clin Exp Res 17:690–695

    Article  PubMed  CAS  Google Scholar 

  3. Crilly RG, Anderson C, Hogan D, Delaquerriere-Richardson L (1988) Bone histomorphometry, bone mass, and related parameters in alcoholic males. Calcif Tissue Int 43:269–276

    Article  PubMed  CAS  Google Scholar 

  4. Nielsen HK, Lundby L, Rasmussen K, Charles P, Hansen C (1990) Alcohol decreases serum osteocalcin in a dose-dependent way in normal subjects. Calcif Tissue Int 46:173–178

    Article  PubMed  CAS  Google Scholar 

  5. Diez A, Puig J, Serrano S, Marinoso ML, Bosch J, Marrugat J, Mellibovsky L, Nogues X, Knobel H, Aubia J (1994) Alcohol-induced bone disease in the absence of severe chronic liver damage. J Bone Miner Res 9:825–831

    Article  PubMed  CAS  Google Scholar 

  6. Lalor BC, France MW, Powell D, Adams PH, Counihan TB (1986) Bone and mineral metabolism and chronic alcohol abuse. QJ Med 59:497–511

    CAS  Google Scholar 

  7. Schnitzler CM, Solomon L (1984) Bone changes after alcohol abuse. S Afr Med J 66:730–734

    PubMed  CAS  Google Scholar 

  8. Harding A, Dunlap J, Cook S, Mattalino A, Azar F, O'Brien M, Kester M (1988) Osteoporotic correlates of alcoholism in young males. Orthopedics 11:279–282

    PubMed  CAS  Google Scholar 

  9. Odvina CV, Safi I, Wojtowicz CH, Barengolts EI, Lathon P, Skapars A, Desai PN, Kukreja SC (1995) Effect of heavy alcohol intake in the absence of liver disease on bone mass in black and white men. J Clin Endocrinol Metabol 80:2499–2503

    Article  CAS  Google Scholar 

  10. Maran A, Zhang M, Spelsberg TC, Turner RT (2001) The dose-response effects of ethanol on the human fetal osteoblastic cell line. J Bone Miner Res 16:270–276

    Article  PubMed  CAS  Google Scholar 

  11. Turner RT, Wronski TJ, Zhang M, Kidder LS, Bloomfield SA, Sibonga JD (1998) Effects of ethanol on gene expression in rat bone: transient dose-dependent changes in mRNA levels for matrix proteins, skeletal growth factors, and cytokines are followed by reductions in bone formation. Alcohol Clin Exp Res 22:1591–1599

    PubMed  CAS  Google Scholar 

  12. Chavassieux P, Serre CM, Vergnaud P, Delmas PD, Meunier PJ (1993) In vitro evaluation of dose-effects of ethanol on human osteoblastic cells. Bone Miner 22:95–103

    Article  PubMed  CAS  Google Scholar 

  13. Klein RF, Fausti KA, Carlos AS (1996) Ethanol inhibits human osteoblastic cell proliferation. Alcohol Clin Exp Res 20:572–578

    Article  PubMed  CAS  Google Scholar 

  14. Turner RT, Kidder LS, Kennedy A, Evans GL, Sibonga JD (2001) Moderate alcohol consumption suppresses bone turnover in adult female rats. J Bone Miner Res 16:589–594

    Article  PubMed  CAS  Google Scholar 

  15. Bikle DD, Genant HK, Cann C, Recker RR, Halloran BP, Strewler GJ (1985) Bone disease in alcohol abuse. Ann Inter Med 103:42–48

    CAS  Google Scholar 

  16. Barragry JM, Long RG, France MW, Wills MR, Boucher BJ, Sherlock S (1979) Intestinal absorption of cholecalciferol in alcoholic liver disease and primary biliary cirrhosis. Gut 20:559–564

    Article  PubMed  CAS  Google Scholar 

  17. Hepner GW, Roginsky M, Moo HF (1976) Abnormal vitamin D metabolism in patients with cirrhosis. Am J Dig Dis 21:527–532

    Article  PubMed  CAS  Google Scholar 

  18. Bouillon R, Auwerx J, Dekeyser L, Fevery J, Lissens W, De Moor P (1984) Serum vitamin D metabolites and their binding protein in patients with liver cirrhosis. J Clin Endocrinol Met 59:86–89

    Article  CAS  Google Scholar 

  19. Cheung RC, Gray C, Boyde A, Jones SJ (1995) Effects of ethanol on bone cells in vitro resulting in increased resorption. Bone 16:143–147

    PubMed  CAS  Google Scholar 

  20. Simon L, Bertrand L, Michel H, Blotman F, Claustre (1975) Osteonecrosis, alcoholism and liver steatosis. Rev Rhum Mal Osteoartic 42:103–108

    PubMed  CAS  Google Scholar 

  21. Suh KT, Kim SW, Roh HL, Youn MS, Jung JS (2005) Decreased osteogenic differentiation of mesenchymal stem cells in alcohol-induced osteonecrosis. Clin Orthop Relat Res 220-225

  22. Wezeman FH, Gong Z (2001) Bone marrow triglyceride accumulation and hormonal changes during long-term alcohol intake in male and female rats. Alcohol Clin Exp Res 25:1515–1522

    Article  PubMed  CAS  Google Scholar 

  23. Kawai M, Devlin MJ, Rosen CJ (2009) Fat targets for skeletal health. Nat Rev Rheumatol 5:365–372

    Article  PubMed  Google Scholar 

  24. Takada I, Kouzmenko AP, Kato S (2009) Molecular switching of osteoblastogenesis versus adipogenesis: implications for targeted therapies. Expert Opin Ther Targets 13:593–603

    Article  PubMed  CAS  Google Scholar 

  25. Dobnig H, Turner RT (1995) Evidence that intermittent treatment with parathyroid hormone increases bone formation in adult rats by activation of bone lining cells. Endocrinology 136:3632–3638

    Article  PubMed  CAS  Google Scholar 

  26. Menagh P, Turner R, Jump D, Wong C, Lowry M, Yakar S, Rosen C, Iwaniec UT (In Press) Growth hormone regulates the balance between bone formation and bone marrow adiposity. J Bone Miner Res PMID: 19821771

  27. Turner RT, Rosen CJ, Iwaniec UT (2010) Effects of alcohol on skeletal response to growth hormone in hypophysectomized rats. Bone 246:806–12

    Article  Google Scholar 

  28. Giustina A, Mazziotti G, Canalis E (2008) Growth hormone, insulin-like growth factors, and the skeleton. Endocr Rev 29:535–559

    Article  PubMed  CAS  Google Scholar 

  29. Maddalozzo GF, Turner RT, Edwards CH, Howe KS, Widrick JJ, Rosen CJ, Iwaniec UT (2009) Alcohol alters whole body composition, inhibits bone formation, and increases bone marrow adiposity in rats. Osteoporos Int 20:1529–1538

    Article  PubMed  CAS  Google Scholar 

  30. Iwaniec UT, Wronski TJ, Turner RT (2008) Histological analysis of bone. Meth Mol Biol 447:325–341

    Article  Google Scholar 

  31. Turner RT (2000) Skeletal response to alcohol. Alcohol Clin Exp Res 24:1693–1701

    Article  PubMed  CAS  Google Scholar 

  32. Sampson HW, Chaffin C, Lange J, DeFee B 2nd (1997) Alcohol consumption by young actively growing rats: a histomorphometric study of cancellous bone. Alcohol Clin Exp Res 21:352–359

    PubMed  CAS  Google Scholar 

  33. Sibonga JD, Iwaniec UT, Shogren KL, Rosen CJ, Turner RT (2007) Effects of parathyroid hormone (1-34) on tibia in an adult rat model for chronic alcohol abuse. Bone 40:1013–1020

    Article  PubMed  CAS  Google Scholar 

  34. Wezeman FH, Emanuele MA, Emanuele NV, Moskal SF 2nd, Woods M, Suri M, Steiner J, LaPaglia N (1999) Chronic alcohol consumption during male rat adolescence impairs skeletal development through effects on osteoblast gene expression, bone mineral density, and bone strength. Alcohol Clin Exp Res 23:1534–1542

    PubMed  CAS  Google Scholar 

  35. Samelson EJ, Hannan MT, Zhang Y, Genant HK, Felson DT, Kiel DP (2006) Incidence and risk factors for vertebral fracture in women and men: 25-year follow-up results from the population-based Framingham study. J Bone Miner Res 21:1207–1214

    Article  PubMed  Google Scholar 

  36. Turner RT, Evans GL, Lotinun S, Lapke PD, Iwaniec UT, Morey-Holton E (2007) Dose-response effects of intermittent PTH on cancellous bone in hindlimb unloaded rats. J Bone Miner Res 22:64–71

    Article  PubMed  CAS  Google Scholar 

  37. Turner RT, Lotinun S, Hefferan TE, Morey-Holton E (2006) Disuse in adult male rats attenuates the bone anabolic response to a therapeutic dose of parathyroid hormone. J Appl Physiol 101:881–886

    Article  PubMed  CAS  Google Scholar 

  38. Lauing K, Himes R, Rachwalski M, Strotman P, Callaci JJ (2008) Binge alcohol treatment of adolescent rats followed by alcohol abstinence is associated with site-specific differences in bone loss and incomplete recovery of bone mass and strength. Alcohol 42:649–656

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by National Institutes of Health grant AA011140 and Department of Defense grant PRO43181 (to R.T. Turner).

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Howe, K.S., Iwaniec, U.T. & Turner, R.T. The effects of low dose parathyroid hormone on lumbar vertebrae in a rat model for chronic alcohol abuse. Osteoporos Int 22, 1175–1181 (2011). https://doi.org/10.1007/s00198-010-1304-4

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  • DOI: https://doi.org/10.1007/s00198-010-1304-4

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