Skip to main content

Advertisement

SpringerLink
Log in

Osteopenia and osteoporosis in gastrointestinal diseases: Diagnosis and treatment

  • Published:
Current Gastroenterology Reports Aims and scope Submit manuscript

Abstract

An increased awareness of the higher incidence of osteopenia and osteoporosis associated with a number of gastrointestinal disease states has occurred over the last few years. High rates of bone loss have been reported in luminal diseases such as inflammatory bowel disease and celiac disease as well as in cholestatic liver diseases and in the post-liver transplant setting. The post-gastrectomy state and chronic pancreatitis are also associated with decreased bone density. Publications over the last year have provided a better understanding of the true incidence of osteoporosis and fracture risk in these gastrointestinal disease states. Dual-energy x-ray absorptiometry remains the diagnostic procedure of choice. Biochemical markers of bone resorption have a role in identifying those patients with ongoing bone loss and monitoring their response to therapy. Identification of patients at risk and initiation of measures to prevent bone loss form the optimal therapeutic strategy. This article reviews advancements in the understanding of the development and activation of osteoblasts and osteoclasts. It also reviews the recent data concerning the diagnosis and treatment of bone loss associated with various gastrointestinal disease states.

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

Similar content being viewed by others

References and Recommended Reading

  1. Ducy P, Schinke T, Karsenty G: The osteoblast: a sophisticated fibroblast under central surveillance. Science 2000, 289:1501–1504. This review concisely summarizes the mechanisms of osteoblast development and activation. Transgenic and molecular studies are explained and placed in the context of normal osteoblast development.

    Article  PubMed  CAS  Google Scholar 

  2. Teitelbaum SL: Bone resorption by osteoclast. Science 2000, 289:1501–1508. This review covers osteoclast development and activation and concisely describes the interaction of stromal cells and osteoblasts in osteoclast development. The mechanism of how osteoclasts break down bone is also reviewed.

    Article  Google Scholar 

  3. Komori T, Yagi H, Nomura S, et al.: Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell 1997, 89:755–764.

    Article  PubMed  CAS  Google Scholar 

  4. Thirunavukkarasu K, Halladay DL, Miles RR, et al.: The osteoblast- specific transcription factor Cbfa1 contributes to the expression of osteoprotegerin, a potent inhibitor of osteoclast differentiation and function. J Biol Chem 2000, 275:25163–25172.

    Article  PubMed  CAS  Google Scholar 

  5. Ducy P, Amling M, Takeda S, et al.: Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. Cell 2000, 100:197–207. This article identifies leptin as a centrally active regulator of bone mass. This may explain the protective effect of obesity in preserving bone mass in humans.

    Article  PubMed  CAS  Google Scholar 

  6. Kong YY, Feige U, Sarosi I, et al.: Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand. Nature 1999, 402:304–309. This article demonstrates that activated T cells can directly stimulate osteoclastogenesis and bone loss, a concept with major implications for the heightened osteoclast activity observed in chronic inflammatory diseases.

    Article  PubMed  CAS  Google Scholar 

  7. Lacey DL, Timms E, Tan HL, et al.: Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 1998, 93:165–176.

    Article  PubMed  CAS  Google Scholar 

  8. Dougall WC, Glaccum M, Charrier K, et al.: RANK is essential for osteoclast and lymph node development. Genes Dev 1999, 13:2412–2424.

    Article  PubMed  CAS  Google Scholar 

  9. Lam J, Takeshita S, Barker JE, et al.: TNF-alpha induces osteoclastogenesis by direct stimulation of macrophages exposed to permissive levels of RANK ligand. J Clin Invest 2000, 106:1481–1488. This article clarifies the role of TNF and possibly other proinflammatory cytokines in stimulation of osteoclastogenesis and bone loss. The authors help to explain the increased osteoclast activity in chronic inflammatory diseases such as inflammatory bowel disease.

    PubMed  CAS  Google Scholar 

  10. Zhang YH, Heulsmann A, Tondravi MM, et al.: Tumor necrosis factor-alpha (TNF) stimulates RANKL-induced osteoclastogenesis via coupling of TNF type 1 receptor and RANK signaling pathways. J Biol Chem 2001, 276:563–568. This article, together with [9], helps to explain how increased TNF production leads to an increase in osteoclast activity. It also describes the role of TNF in the increased osteoclast activity in chronic inflammatory diseases.

    Article  PubMed  CAS  Google Scholar 

  11. Frost ML, Blake GM, Fogelman I: Quantitative ultrasound and bone mineral density are equally strongly associated with factors for osteoporosis. J Bone Miner Res 2001, 16:406–416.

    Article  PubMed  CAS  Google Scholar 

  12. Cetin A, Erturk H, Celiker R, et al.: The role of quantitative ultrasound in predicting osteoporosis defined by dual X-ray absorptiometry. Rheumatol Int 2001, 20:55–59.

    Article  Google Scholar 

  13. Jahnsen J, Falch JA, Mowinckel P, Aadland E: Ultrasound measurements of calcaneous for estimation of skeletal status in patients with inflammatory bowel disease. Scand J Gastroenterol 1999, 34:790–797.

    Article  PubMed  CAS  Google Scholar 

  14. Fogelman I, Blake GM: Different approaches to bone densitometry. J Nucl Med 2000, 41:2015–2025.

    PubMed  CAS  Google Scholar 

  15. Kyd PA, De Vooght K, Kerkhoff F, et al.: Clinical usefulness of biochemical resorption markers in osteoporosis. Ann Clin Biochem 1999, 36:483–491.

    PubMed  Google Scholar 

  16. Greenspan SL, Rosen HN, Parker RA: Early changes in serum N-telopeptide and C-telopeptide cross-linked collagen type 1 predict long-term response to alendronate therapy in elderly women. J Clin Endocrinol Metab 2000, 85:3537–3540.

    Article  PubMed  CAS  Google Scholar 

  17. Dresner-Pollack R, Darmeli F, Eliakim R, et al.: Increased urinary N-telopeptide cross-linked type 1 collagen predicts bone loss in patients with inflammatory bowel disease. Am J Gastroenterol 2000, 95:699–704.

    Article  Google Scholar 

  18. Bjarnason I, Macpherson C, Buxton-Thomas M: Reduced bone mineral density in patients with inflammatory bowel disease. Gut 1997, 40:228–233.

    PubMed  CAS  Google Scholar 

  19. Dresner-Pollack R, Karmeli F, Eliakim R, et al.: Femoral neck osteopenia in patients with inflammatory bowel disease. Am J Gastroenterol 1998, 93:1483–1490.

    Article  Google Scholar 

  20. Andreassen H, Rungby J, Dahlerup JF: Inflammatory bowel disease and osteoporosis. Scand J Gastroenterol 1997, 32:1247–1255.

    PubMed  CAS  Google Scholar 

  21. Ardizzone S, Bollani S, Bettica P, et al.: Altered bone metabolism in inflammatory bowel disease: there is a difference between Crohn's disease and ulcerative colitis. J Int Med 2000, 247:63–70.

    Article  CAS  Google Scholar 

  22. Bernstein CN, Blanchard JF, Leslie W, et al.: The incidence of fracture among patients with inflammatory bowel disease: a population cohort study. Ann Int Med 2000, 133:795–799. This large population-based study revealed a fracture rate among patients with inflammatory bowel disease that was 40% higher than that in matched cohorts. Increased fracture incidence was seen in the spine, hip, wrist/forearm, and ribs.

    PubMed  CAS  Google Scholar 

  23. Vestergaard P, Krogh K, Rejnmark L, et al.: Fracture risk is increased in Crohn's disease, but not in ulcerative colitis. Gut 2000, 46:176–181.

    Article  PubMed  CAS  Google Scholar 

  24. Manolagas SC, Jilka RL: Bone marrow, cytokines, and bone remodeling: emerging insights into the pathophysiology of osteoporosis. N Engl J Med 1995, 332:305–311.

    Article  PubMed  CAS  Google Scholar 

  25. Armour KE, Van'T Hof RJ, Grabowski PS, et al.: Evidence for a pathogenic role of nitric oxide in inflammation-induced osteoporosis. J Bone Miner Res 1999, 14:2137–2142.

    Article  PubMed  CAS  Google Scholar 

  26. Silverberg MS, Mikoalainis S, Steinhart AH: Low bone mineral density (BMD) in Crohn's disease (CD) occurs independent of corticosteroid use [abstract]. Gastroenterology 1998, 114:A1086.

    Article  Google Scholar 

  27. Ghosh S, Cowen S, Hannan WJ, Ferguson A: Low bone mineral density in Crohn's disease, but not in ulcerative colitis at diagnosis. Gastroenterology 1994, 107:1031–1039.

    PubMed  CAS  Google Scholar 

  28. Schoon EJ, Blok BM, Geerling BJ, et al.: Bone mineral density in patients with recently diagnosed inflammatory bowel disease. Gastroenterology 2000, 119:1203–1208.

    Article  PubMed  CAS  Google Scholar 

  29. Kemppainen T, Kroger H, Janatuinen E, et al.: Osteoporosis in adult patients with celiac disease. Bone 1999, 24:249–255.

    Article  PubMed  CAS  Google Scholar 

  30. Meyer D, Stavropolous S, Diamond B, Shane E: Osteoporosis in a North American adult population with celiac disease. Am J Gastroenterol 2001, 96:112–119.

    PubMed  CAS  Google Scholar 

  31. Vazquez H, Mazure R, Gonzales D: Risk of fractures in celiac disease patients: a cross-sectional, case-control study. Am J Gastroenterol 2000, 95:183–189. This study reported a high prevalence of peripheral fractures in a large cohort of celiac patients. Eighty percent of fractures occurred before disease diagnosis, emphasizing the importance of screening newly diagnosed patients for bone disease.

    Article  Google Scholar 

  32. Selby PL, Davies M, Adams JE, Mawer EB: Bone loss in celiac disease is related to secondary hyperparathyroidism. J Bone Miner Res 1999, 14:652–657.

    Article  PubMed  CAS  Google Scholar 

  33. Fornari MC, Pedreira S, Niveloni S: Pre- and post-treatment serum levels of cytokines IL-1b, IL-6 and IL-1 receptor antagonist in celiac disease: are they related to the associated osteopenia? Am J Gastroenterol 1998, 93:413–418.

    PubMed  CAS  Google Scholar 

  34. Janes CH, Dickson ER, Okazaki R, et al.: Role of hyperbilirubinemia in the impairment of osteoblast proliferation associated with cholestatic jaundice. J Clin Invest 1995, 95:2581–2586.

    Article  PubMed  CAS  Google Scholar 

  35. Trautwein C, Possienke M, Schlitt HJ, et al.: Bone density and metabolism in patients with viral hepatitis and cholestatic liver disease before and after liver transplantation. Am J Gastroenterol 2000, 95:2343–2351.

    Article  PubMed  CAS  Google Scholar 

  36. Shiomi S, Masaki K, Habu D, et al.: Calcitriol for bone loss in patients with primary biliary cirrhosis. J Gastroenterol 1999, 34:241–245.

    Article  PubMed  CAS  Google Scholar 

  37. Ninkovic M, Skingle SJ, Bearcroft PW, et al.: Incidence of vertebral fracture in the first three months after orthotopic liver transplantation. Eur J Gastroenterol Hepatol 2000, 12:931–935.

    Article  PubMed  CAS  Google Scholar 

  38. Leidig-Bruckner G, Hosch S, Dodidou P, et al.: Frequency and predictors of osteoporotic fractures after cardiac or liver transplantation: a follow-up study. Lancet 2001, 357:342–347.

    Article  PubMed  CAS  Google Scholar 

  39. Giannini S, Nobile M, Ciuffreda M, et al.: Long-term persistence of low bone density in orthotopic liver transplantation. Osteoporosis 2000, 11:417–424.

    Article  CAS  Google Scholar 

  40. Adachi Y, Shiota E, Matsumata T, Iso Y, et al.: Osteoporosis after gastrectomy: bone mineral density of lumbar spine assessed by dual-energy X-ray absorptiometry. Calcif Tissue Int 2000, 66:119–122.

    Article  PubMed  CAS  Google Scholar 

  41. Heiskanen JT, Kroger H, Paakkonen M, et al.: Bone mineral metabolism after total gastrectomy. Bone 2001, 28:123–127.

    Article  PubMed  CAS  Google Scholar 

  42. Moran CE, Sosa EG, Martinez SM, et al.: Bone mineral density in patients with pancreatic insufficiency and steatorrhea. Am J Gastroenterol 1997, 92:867–871.

    PubMed  CAS  Google Scholar 

  43. Haaber AB, Rosenfalck AM, Hansen B, et al.: Bone mineral metabolism, bone mineral density, and body composition in patients with chronic pancreatitis and pancreatic exocrine insufficiency. Int J Pancreatol 2000, 27:21–27.

    PubMed  CAS  Google Scholar 

  44. Valentine JF, Sninsky CA: Prevention and treatment of osteoporosis in patients with inflammatory bowel disease. Am J Gastroenterol 1999, 94:878–883.

    Article  PubMed  CAS  Google Scholar 

  45. Scott EM, Gaywood I, Scott BB: Guidelines for osteoporosis in coeliac disease and inflammatory bowel disease. Gut 2000, 46(suppl 1):11–18.

    Article  Google Scholar 

  46. Robinson RJ, Krzywicki T, Almond L, et al.: Effect of low-impact exercise program on bone mineral density in Crohn's disease: a randomized controlled trial. Gastroenterology 1998, 115:36–41.

    Article  PubMed  CAS  Google Scholar 

  47. Recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis. American College of Rheumatology Task Force on Osteoporosis Guidelines. Arthritis Rheum 1996, 39:1791–1801.

  48. Sategna-Guidetti C, Grosso S, Mengozzi G, et al.: The effects of 1-year gluten withdrawal on bone mass, bone metabolism and nutritional status in newly-diagnosed adult coeliac disease patients. Aliment Pharmacol Ther 2000, 14:35–43.

    Article  PubMed  CAS  Google Scholar 

  49. Rodan GA, Martin TH: Therapeutic approaches to bone diseases. Science 2000, 289:1508–1514. This review explains how therapeutic agents for the treatment of osteoporosis interact with the mechanisms of osteoclast development and activation. Potential new therapeutic targets are discussed.

    Article  PubMed  CAS  Google Scholar 

  50. Clements D, Compston JE, Evans WD: Hormone replacement therapy prevents bone loss in patients with inflammatory bowel disease. Gut 1993, 34:1543–1546.

    PubMed  CAS  Google Scholar 

  51. Olsson R, Mattsson LA, Obrant K, Mellstrom D: Estrogenprogesterone therapy for low bone mineral density in primary biliary cirrhosis. Liver 1999, 19:188–192.

    Article  PubMed  CAS  Google Scholar 

  52. Camisasca M, Crosignani A, Battezzati PM, et al.: Parenteral calcitonin for metabolic bone disease associated with primary biliary cirrhosis. Hepatology 1994, 20:633–637.

    Article  PubMed  CAS  Google Scholar 

  53. Floreani A, Zappala F, Fries W, et al.: A 3-year pilot study with 1,25-dihydroxyvitamin D, calcium, and calcitonin for severe osteodystrophy in primary biliary cirrhosis. J Clin Gastroenterol 1997, 24:239–244.

    Article  PubMed  CAS  Google Scholar 

  54. Hay JE, Malinchoc M, Dickson ER: A controlled trial of calcitonin therapy for the prevention of post-liver transplantation atraumatic fractures in patients with primary biliary cirrhosis and primary sclerosing cholangitis. J Hepatol 2001, 34:292–298.

    Article  PubMed  CAS  Google Scholar 

  55. Downs RW Jr, Bell NH, Ettinger MP, et al.: Comparison of alendronate and intranasal calcitonin for treatment of osteoporosis in postmenopausal women. J Clin Endocrinol Metab 2000, 85:1783–1788.

    Article  PubMed  CAS  Google Scholar 

  56. Saag KG, Emkey R, Schnitzer TJ, et al.: Alendronate for the prevention and treatment of glucocorticoid induced osteoporosis. N Engl J Med 1998, 339:292–299.

    Article  PubMed  CAS  Google Scholar 

  57. Cohen S, Levy RM, Keller M, et al.: Risedronate therapy prevents corticosteroid-induced bone loss: a twelve month, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Arthritis Rheum 1999, 42:2309–2318.

    Article  PubMed  CAS  Google Scholar 

  58. Haderlev KV, Tjellsen L, Sorensen HA, Staun M: Alendronate increases lumbar spine bone density in patients with Crohn's disease. Gastroenterology 2000, 119:639–646.

    Article  Google Scholar 

  59. Wolfhagen FH, van Buren HR, den Ouden JW, et al.: Cyclical etidronate in the prevention of bone loss in corticosteroidtreated primary biliary cirrhosis: a prospective, controlled pilot study. J Hepatol 1997, 26:325–330.

    Article  PubMed  CAS  Google Scholar 

  60. Lindor KD, Jorgensen RA, Tiegs RD, et al.: Etidronate for osteoporosis in primary biliary cirrhosis: a randomized trial. J Hepatol 2000, 33:878–882.

    Article  PubMed  CAS  Google Scholar 

  61. Reeves HL, Francis RM, Manas DM, et al.: Intravenous bisphosphonate prevents symptomatic osteoporotic vertebral collapse in patients after liver transplantation. Liver Transpl Surg 1998, 4:404–409.

    Article  PubMed  CAS  Google Scholar 

  62. Von Tirpitz C, Bruckel J, Rieber A, et al.: Increase in bone mineral density with sodium fluoride in patients with Crohn's disease. Eur J Gastroenterol Hepatol 2000, 12:19–24. In this study, significant increases in lumbar bone density were achieved in 33 Crohn's disease patients treated with low-dose sodium fluoride in combination with calcium and vitamin D supplementation. Calcium and vitamin D supplementation alone did not result in significant increases in lumbar bone density over the one year of treatment.

    Google Scholar 

  63. Riggs BL, Hodgson SF, O'Fallon WM, et al.: Effect of fluoride treatment on the fracture rate in post-menopausal women with osteoporosis. N Engl J Med 1990, 322:802–809.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Gastroenterology, Hepatology, and Nutrition, University of Florida and Malcom Randall VA Medical Center, Box 100214, 32610, Gainesville, FL, USA

    John C. Southerland MD & John F. Valentine MD

Authors
  1. John C. Southerland MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. John F. Valentine MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Southerland, J.C., Valentine, J.F. Osteopenia and osteoporosis in gastrointestinal diseases: Diagnosis and treatment. Curr Gastroenterol Rep 3, 399–407 (2001). https://doi.org/10.1007/s11894-001-0082-8

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11894-001-0082-8

Keywords

Search

Navigation