Osteoporosis International

, Volume 17, Issue 12, pp 1707–1715 | Cite as

Osteoporosis prevention and therapy: preserving and building strength through bone quality

Review

Abstract

While bone mineral density measurements play a central role in osteoporosis management, the degree to which increases in this parameter contribute to bone fragility, fracture risk, and the therapeutic efficacy of osteoporosis agents is controversial. Indeed, bone strength is also significantly dependent upon bone turnover and bone quality, including microarchitecture, mineralization, and geometry. Given the critical role of these factors, it is essential to understand how they are affected by therapeutic agents. Even though a number of technological advances, such as microcomputed tomography, magnetic resonance imaging, and computerized analysis of radiographic patterns, help to provide critical information toward a more comprehensive assessment of bone turnover and bone quality, clinical trials addressing these factors are scarce. This article provides a review of studies relating to how osteoporosis therapies impact parameters of bone strength and quality.

Keywords

Bisphosphonates Calcitonin Estrogen and SERMs Osteoporosis Parathyroid hormone 

References

  1. 1.
    Hochberg MC, Greenspan S, Wasnich RD, Miller P, Thompson DE, Ross PD (2002) Changes in bone density and turnover explain the reductions in incidence of nonvertebral fractures that occur during treatment with antiresorptive agents. J Clin Endocrinol Metab 87:1586–1592PubMedCrossRefGoogle Scholar
  2. 2.
    Wasnich RD, Miller PD (2000) Antifracture efficacy of antiresorptive agents are related to change in bone density. J Clin Endocrinol Metab 85:231–236PubMedCrossRefGoogle Scholar
  3. 3.
    Cummings SR, Karpf DB, Harris F, Genant HK, Ensrud K, LaCroix AZ et al (2002) Improvement in spine bone density and reduction in risk of vertebral fractures during treatment with antiresorptive drugs. Am J Med 112:281–289PubMedCrossRefGoogle Scholar
  4. 4.
    Delmas PD, Seeman E (2004) Changes in bone mineral density explain little of the reduction in vertebral or nonvertebral fracture risk with anti-resorptive therapy. Bone 34:599–604PubMedCrossRefGoogle Scholar
  5. 5.
    Cefalu CA (2004) Is bone mineral density predictive of fracture risk reduction? Curr Med Res Opin 20:341–349PubMedCrossRefGoogle Scholar
  6. 6.
    National Osteoporosis Foundation (2003) Disease statistics “fast facts”. National Osteoporosis Foundation, Washington, D.C., pp 1–7Google Scholar
  7. 7.
    National Osteoporosis Foundation (2002) America’s bone health: the state of osteoporosis and low bone mass in our nation. National Osteoporosis Foundation, Washington, DC, pp 1–55Google Scholar
  8. 8.
    Seeman E (2003) The structural and biomechanical basis of the gain and loss of bone strength in women and men. Endocrinol Metab Clin North Am 32:25–38PubMedCrossRefGoogle Scholar
  9. 9.
    Manolagas SC (2000) Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis. Endocr Rev 21:115–137PubMedCrossRefGoogle Scholar
  10. 10.
    Andrade SE, Majumdar SR, Chan A, Buist DSM, Go AS, Goodman M et al (2003) Low frequency of treatment of osteoporosis among postmenopausal women following a fracture. Arch Intern Med 163:2052–2057PubMedCrossRefGoogle Scholar
  11. 11.
    Parfitt AM, Mundy GR, Roodman GD, Hughes DE, Boyce BF (1996) A new model for the regulation of bone resorption, with particular reference to the effects of bisphosphonates. J Bone Miner Res 11:150–159PubMedGoogle Scholar
  12. 12.
    Manolagas SC, Kousteni S, Jilka RL (2002) Sex steroids and bone. Recent Prog Horm Res 57:385–409PubMedCrossRefGoogle Scholar
  13. 13.
    Vaananen HK, Harkonen PL (1996) Estrogen and bone metabolism. Maturitas 23 Suppl:S65–S69PubMedGoogle Scholar
  14. 14.
    Cauley JA, Seeley DG, Ensrud K, Ettinger B, Black D, Cummings SR et al (1995) Estrogen replacement therapy and fractures in older women. Ann Intern Med 122:9–16PubMedGoogle Scholar
  15. 15.
    Schneider DL, Barrett-Connor EL, Morton DJ (1997) Timing of postmenopausal estrogen for optimal bone mineral density. The Rancho Bernardo Study. JAMA 277:543–547PubMedCrossRefGoogle Scholar
  16. 16.
    Barrett-Connor E, Wehren LE, Yates J, Brenneman SK, Chen Y-T, Siris ES (2003) Rapid loss of hip anatifracture efficacy following estrogen cessation: evidence from NORA. Obstet Gynecol 4 (suppl 5):5s (Abstract)CrossRefGoogle Scholar
  17. 17.
    Greenspan SL, Emkey RD, Bone HG, III, Weiss SR, Bell NH, Downs RW Jr et al (2002) Significant differential effects of alendronate, estrogen, or combination therapy on the rate of bone loss after discontinuation of treatment of postmenopausal osteoporosis. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 137:875–883PubMedGoogle Scholar
  18. 18.
    Banks E, Beral V, Reeves G, Balkwill A, Barnes I (2004) Fracture incidence in relation to the pattern of use of hormone therapy in postmenopausal women. JAMA 291:2212–2220PubMedCrossRefGoogle Scholar
  19. 19.
    Jackson RD, Watts NB, Caralis P, Cauley JA, Chen Z, Greep N et al (2004) Fracture risk after estrogen plus progestin discontinuation: the Women’s Health Initiative. J Bone Miner Res 19:S27 (Abstract)Google Scholar
  20. 20.
    Lindsay R, Gallagher JC, Kleerekoper M, Pickar JH (2002) Effect of lower doses of conjugated equine estrogens with and without medroxyprogesterone acetate on bone in early postmenopausal women. JAMA 287:2668–2676PubMedCrossRefGoogle Scholar
  21. 21.
    Cauley JA, Robbins J, Chen Z, Cummings SR, Jackson RD, LaCroix AZ et al (2003) Effects of estrogen plus progestin on risk of fracture and bone mineral density: the Women’s Health Initiative randomized trial. JAMA 290:1729–1738PubMedCrossRefGoogle Scholar
  22. 22.
    Women’s Health Initiative Steering Committee (2004) Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women’s Health Initiative randomized controlled trial. JAMA 291:1701–1712CrossRefGoogle Scholar
  23. 23.
    Grady D, Herrington D, Bittner V, Blumenthal R, Davidson M, Hlatky M et al (2002) Cardiovascular disease outcomes during 6.8 years of hormone therapy: heart and estrogen/progestin replacement study follow-up (HERS II). JAMA 288:49–57PubMedCrossRefGoogle Scholar
  24. 24.
    Hulley S, Furberg C, Barrett-Connor E, Cauley J, Grady D, Haskell W et al (2002) Noncardiovascular disease outcomes during 6.8 years of hormone therapy: heart and estrogen/progestin replacement study follow-up (HERS II). JAMA 288:58–66PubMedCrossRefGoogle Scholar
  25. 25.
    Writing Group for the Women’s Health Initiative Investigators (2002) Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial. JAMA 288:321–333CrossRefGoogle Scholar
  26. 26.
    US Food and Drug Administration (2003) Menopause & hormones. http://www.fda.gov/default.htm
  27. 27.
    Eriksen EF, Langdahl B, Vesterby A, Rungby J, Kassem M (1999) Hormone replacement therapy prevents osteoclastic hyperactivity: a histomorphometric study in early postmenopausal women. J Bone Miner Res 14:1217–1221PubMedCrossRefGoogle Scholar
  28. 28.
    Paschalis EP, Boskey AL, Kassem M, Eriksen EF (2003) Effect of hormone replacement therapy on bone quality in early postmenopausal women. J Bone Miner Res 18:955–959PubMedCrossRefGoogle Scholar
  29. 29.
    Khastgir G, Studd J, Holland N, Alaghband-Zadeh J, Sims TJ, Bailey AJ (2001) Anabolic effect of long-term estrogen replacement on bone collagen in elderly postmenopausal women with osteoporosis. Osteoporos Int 12:465–470PubMedCrossRefGoogle Scholar
  30. 30.
    Vedi S, Bell KL, Loveridge N, Garrahan N, Purdie DW, Compston JE (2003) The effects of hormone replacement therapy on cortical bone in postmenopausal women. A histomorphometric study. Bone 33:330–334PubMedCrossRefGoogle Scholar
  31. 31.
    Bare SJ, Recker S, Recker R, Kimmel D (2005) Influence of estrogen ststus and alendronate on periosteal bone formation in the ilium of adult women. J Bone Miner Res 20:S56 (Abstract)Google Scholar
  32. 32.
    Greenspan SL, Beck TJ, Resnick NM, Bhattacharya R, Parker RA (2005) Effect of hormone replacement, alendronate, or combination therapy on hip structural geometry: a 3-year, double-blind, placebo-controlled clinical trial. J Bone Miner Res 20:1525–1532PubMedCrossRefGoogle Scholar
  33. 33.
    Avioli LV (1998) The role of calcitonin in the prevention of osteoporosis. Endocrinol Metab Clin North Am 27:411–418PubMedCrossRefGoogle Scholar
  34. 34.
    Mehta NM, Malootian A, Gilligan JP (2003) Calcitonin for osteoporosis and bone pain. Curr Pharm Des 9:2659–2676PubMedCrossRefGoogle Scholar
  35. 35.
    Farley JR, Hall SL, Herring S, Tarbaux NM (1992) Two biochemical indices of mouse bone formation are increased, in vivo, in response to calcitonin. Calcif Tissue Int 50:67–73PubMedCrossRefGoogle Scholar
  36. 36.
    Monier-Faugere MC, Geng Z, Qi Q, Arnala I, Malluche HH (1996) Calcitonin prevents bone loss but decreases osteoblastic activity in ovariohysterectomized beagle dogs. J Bone Miner Res 11:446–455PubMedGoogle Scholar
  37. 37.
    Wallach S, Rousseau G, Martin L, Azria M (1999) Effects of calcitonin on animal and in vitro models of skeletal metabolism. Bone 25:509–516PubMedCrossRefGoogle Scholar
  38. 38.
    Gruber HE, Ivey JL, Baylink DJ, Matthews M, Nelp WB, Sisom K et al (1984) Long-term calcitonin therapy in postmenopausal osteoporosis. Metabolism 33:295–303PubMedCrossRefGoogle Scholar
  39. 39.
    Alexandre C, Chappard D, Caulin F, Bertrand A, Palle S, Riffat G (1988) Effects of a one-year administration of phosphate and intermittent calcitonin on bone-forming and bone-resorbing cells in involutional osteoporosis: a histomorphometric study. Calcif Tissue Int 42:345–350PubMedGoogle Scholar
  40. 40.
    Marie PJ, Caulin F (1986) Mechanisms underlying the effects of phosphate and calcitonin on bone histology in postmenopausal osteoporosis. Bone 7:17–22PubMedCrossRefGoogle Scholar
  41. 41.
    Plotkin LI, Weinstein RS, Parfitt AM, Roberson PK, Manolagas SC, Bellido T (1999) Prevention of osteocyte and osteoblast apoptosis by bisphosphonates and calcitonin. J Clin Invest 104:1363–1374PubMedCrossRefGoogle Scholar
  42. 42.
    Boivin GY, Chavassieux PM, Santora AC, Yates J, Meunier PJ (2000) Alendronate increases bone strength by increasing the mean degree of mineralization of bone tissue in osteoporotic women. Bone 27:687–694PubMedCrossRefGoogle Scholar
  43. 43.
    Marx RE (2003) Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. J Oral Maxillofac Surg 61:1115–1117PubMedCrossRefGoogle Scholar
  44. 44.
    Ruggiero SL, Mehrotra B, Rosenberg TJ, Engroff SL (2004) Osteonecrosis of the jaws associated with the use of bisphosphonates: a review of 63 cases. J Oral Maxillofac Surg 62:527–534PubMedCrossRefGoogle Scholar
  45. 45.
    Woo S-B, Hellstein JW, Kalmar JR (2006) Systematic review: bisphosphonates and osteonecrosis of the jaws. Ann Intern Med 144:753–761PubMedGoogle Scholar
  46. 46.
    Marx RE, Sawatari Y, Fortin M, Broumand V (2005) Bisphosphonate-induced exposed bone (osteonecrosis/osteopetrosis) of the jaws: risk factors, recognition, prevention, and treatment. J Oral Maxillofac Surg 63:1567–1575PubMedCrossRefGoogle Scholar
  47. 47.
    Durie BG, Katz M, Crowley J (2005) Osteonecrosis of the jaw and bisphosphonates. N Engl J Med 353:99–102PubMedCrossRefGoogle Scholar
  48. 48.
    Ruggiero S, Gralow J, Marx RE, Hoff AO, Schubert MM, Huryn JM et al (2006) Practical guidelines for the prevention, diagnosis and treatment of osteonecrosis of the jaw in patients with cancer. J Oncology Practice 2:7–14Google Scholar
  49. 49.
    Roschger P, Rinnerthaler S, Yates J, Rodan GA, Fratzl P, Klaushofer K (2001) Alendronate increases degree and uniformity of mineralization in cancellous bone and decreases the porosity in cortical bone of osteoporotic women. Bone 29:185–191PubMedCrossRefGoogle Scholar
  50. 50.
    Odvina CV, Zerwekh JE, Rao DS, Maalouf N, Gottschalk FA, Pak CY (2005) Severely suppressed bone turnover: a potential complication of alendronate therapy. J Clin Endocrinol Metab 90:1294–1301PubMedCrossRefGoogle Scholar
  51. 51.
    Woo SB, Hellstein JW, Kalmar JR (2006) Systematic review: bisphosphonates and osteonecrosis of the jaws. Ann Intern Med 144:753–761PubMedGoogle Scholar
  52. 52.
    Food and Drug Adminstration (2004) ODS Postmarketing Safety Review. http://www.fda.gov/ohrms/dockets/ac/05/briefing/2005-4095B2_03_04-FDA-TAB3.pdf
  53. 53.
    Dufresne TE, Chmielewski PA, Manhart MD, Johnson TD, Borah B (2003) Risedronate preserves bone architecture in early postmenopausal women In 1 year as measured by three-dimensional microcomputed tomography. Calcif Tissue Int 73:423–432PubMedCrossRefGoogle Scholar
  54. 54.
    Borah B, Dufresne TE, Chmielewski PA, Johnson TD, Chines A, Manhart MD (2004) Risedronate preserves bone architecture in postmenopausal women with osteoporosis as measured by three-dimensional microcomputed tomography. Bone 34:736–746PubMedCrossRefGoogle Scholar
  55. 55.
    Recker R, Masarachia P, Santora A, Howard T, Chavassieux P, Arlot M et al (2005) Trabecular bone microarchitecture after alendronate treatment of osteoporotic women. Curr Med Res Opin 21:185–194PubMedCrossRefGoogle Scholar
  56. 56.
    Bone HG, Hosking D, Devogelaer JP, Tucci JR, Emkey RD, Tonino RP et al (2004) Ten years’ experience with alendronate for osteoporosis in postmenopausal women. N Engl J Med 350:1189–1199PubMedCrossRefGoogle Scholar
  57. 57.
    Riggs BL, Hartmann LC (2003) Selective estrogen-receptor modulators-mechanisms of action and application to clinical practice. N Engl J Med 348:618–629PubMedCrossRefGoogle Scholar
  58. 58.
    Ettinger B, Black DM, Mitlak BH, Knickerbocker RK, Nickelsen T, Genant HK et al (1999) Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene. Results from a 3-year randomized clinical trial. JAMA 282:637–645PubMedCrossRefGoogle Scholar
  59. 59.
    Cohen FJ, Lu Y (2000) Characterization of hot flashes reported by healthy postmenopausal women receiving raloxifene or placebo during osteoporosis prevention trials. Maturitas 34:65–73PubMedCrossRefGoogle Scholar
  60. 60.
    Glusman JE, Huster WJ, Paul S (1998) Raloxifene effects on vasomotor and other climacteric symptoms in postmenopausal women. Primary Care Update for Obstetricians and Gynecologists 5:166CrossRefGoogle Scholar
  61. 61.
    Delmas PD, Ensrud KE, Adachi JD, Harper KD, Sarkar S, Gennari C et al (2002) Efficacy of raloxifene on vertebral fracture risk reduction in postmenopausal women with osteoporosis: four-year results from a randomized clinical trial. J Clin Endocrinol Metab 87:3609–3617PubMedCrossRefGoogle Scholar
  62. 62.
    Grady D, Ettinger B, Moscarelli E, Plouffe L Jr, Sarkar S, Ciaccia A et al (2004) Safety and adverse effects associated with raloxifene: multiple outcomes of raloxifene evaluation. Obstet Gynecol 104:837–844PubMedGoogle Scholar
  63. 63.
    Ke HZ, Foley GL, Simmons HA, Shen V, Thompson DD (2004) Long-term treatment of lasofoxifene preserves bone mass and bone strength and does not adversely affect the uterus in ovariectomized rats. Endocrinology 145:1996–2005PubMedCrossRefGoogle Scholar
  64. 64.
    Gruber C, Gruber D (2004) Bazedoxifene (Wyeth). Curr Opin Invest Drugs 5:1086–1093Google Scholar
  65. 65.
    Kharode YP, Green PD, Marzolf JT, Murrills RJ, Bodine PVN, Komm BS et al (2003) Comparison of the effects of bazedoxifene, raloxifene, lasofoxifene and risedronate co-treatment of hPTH-Induced reversal of established osteopenia in ovariectomized rats. J Bone Miner Res 18(suppl 2):S273 (Abstract)Google Scholar
  66. 66.
    Komm B, Kharode Y, Bex F (2002) Bazedoxifene acetate, a new tissue selective estrogen, preserves skeletal mass and vertebral compressive strength in the ovariectomized rat model (ovx) of osteopenia without uterine liability. Osteoporos Int 13(suppl 1):S38–S39 (Abstract)Google Scholar
  67. 67.
    Weinstein RS (2003) Effects of raloxifene, hormone replacement therapy, and placebo on bone turnover in postmenopausal women. Osteoporos Int 14:814–822PubMedCrossRefGoogle Scholar
  68. 68.
    Ott SM, Oleksik A, Lu Y, Harper K, Lips P (2002) Bone histomorphometric and biochemical marker results of a 2-year placebo-controlled trial of raloxifene in postmenopausal women. J Bone Miner Res 17:341–348PubMedCrossRefGoogle Scholar
  69. 69.
    Boivin G, Lips P, Ott SM, Harper KD, Sarkar S, Pinette KV et al (2003) Contribution of raloxifene and calcium and vitamin d(3) supplementation to the increase of the degree of mineralization of bone in postmenopausal women. J Clin Endocrinol Metab 88:4199–4205PubMedCrossRefGoogle Scholar
  70. 70.
    Genant HK, Lang T, Fuerst T, Pinette KV, Zhou C, Thiebaud D et al (2004) Treatment with raloxifene for 2 years increases vertebral bone mineral density as measured by volumetric quantitative computed tomography. Bone 35:1164–1168PubMedCrossRefGoogle Scholar
  71. 71.
    Jiang Y, Zhao JJ, Mitlak BH, Wang O, Genant HK, Eriksen EF (2003) Recombinant human parathyroid hormone (1–34) [teriparatide] improves both cortical and cancellous bone structure. J Bone Miner Res 18:1932–1941PubMedCrossRefGoogle Scholar
  72. 72.
    Uusi-Rasi K, Semanick LM, Zanchetta JR, Bogado CE, Eriksen EF, Sato M et al (2005) Effects of teriparatide [rhPTH {1–34)] treatment on structural geometry of the proximal femur in elderly osteoporotic women. Bone 36:948–958PubMedCrossRefGoogle Scholar
  73. 73.
    Meunier PJ, Roux C, Seeman E, Ortolani S, Badurski JE, Spector TD et al (2004) The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis. N Engl J Med 350:459–468PubMedCrossRefGoogle Scholar
  74. 74.
    Rizzoli R (2005) A new treatment for post-menopausal osteoporosis: strontium ranelate. J Endocrinol Invest 28:50–57PubMedGoogle Scholar
  75. 75.
    Reginster JY, Seeman E, de Vernejoul MC, Adami S, Compston J, Phenekos C et al (2005) Strontium ranelate reduces the risk of nonvertebral fractures in postmenopausal women with osteoporosis: Treatment of Peripheral Osteoporosis (TROPOS) Study. J Clin Endocrinol Metab 90:2816–2822PubMedCrossRefGoogle Scholar
  76. 76.
    Ammann P, Shen V, Robin B, Mauras Y, Bonjour JP, Rizzoli R (2004) Strontium ranelate improves bone resistance by increasing bone mass and improving architecture in intact female rats. J Bone Miner Res 19:2012–2020PubMedCrossRefGoogle Scholar
  77. 77.
    Boivin G, Deloffre P, Perrat B, Panczer G, Boudeulle M, Mauras Y et al (1996) Strontium distribution and interactions with bone mineral in monkey iliac bone after strontium salt (S 12911) administration. J Bone Miner Res 11:1302–1311PubMedCrossRefGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2006

Authors and Affiliations

  1. 1.Department of Internal MedicineSaint Joseph Mercy HospitalAnn ArborUSA

Personalised recommendations