Osteoporosis International

, Volume 21, Issue 6, pp 957–967 | Cite as

PTH improves titanium implant fixation more than pamidronate or renutrition in osteopenic rats chronically fed a low protein diet

  • R. Dayer
  • T. C. Brennan
  • R. Rizzoli
  • P. Ammann
Original Article



We evaluated the effects of parathyroid hormone (PTH), pamidronate, or renutrition on osseointegration of titanium implants in the proximal tibia of rats subject to prolonged low-protein diets. PTH improved mechanical fixation, microarchitecture, and increased pull-out strength. Pamidronate or renutrition had lesser effects. PTH can thus improve implant osseointegration in protein-malnourished rats.


Protein malnutrition impairs implant osseointegration in rats. PTH and pamidronate prevent deleterious effects of protein restriction introduced just prior to implantation. Whether these treatments improve osseointegration after chronic protein deprivation, i.e., in osteopenic bone at time of implantation, is unknown. We evaluated effects of PTH, pamidronate, or renutrition on resistance to pull-out of titanium rods implanted into the rat tibiae following isocaloric low-protein intake.


Forty-one adult female rats received normal or isocaloric low-protein diets. Six weeks later, implants were surgically inserted into proximal tibiae. Following implantation, rats on low-protein diets were treated with PTH (1-34), pamidronate, saline vehicle, or normal protein diets, for another 8 weeks. Tibiae were removed for micro-computerised tomographic morphometry and evaluation of pull-out strength.


Pull-out strength decreased in rats on isocaloric low-protein diets compared with normal protein group (−33.4%). PTH increased pull-out strength in low-protein group, even compared to controls from the normal protein group. PTH and pamidronate increased bone volume/tissue volume, bone-to-implant contact, and trabecular thickness, whilst trabecular separation was reduced, with a shift to more plate-like bone surrounding the implants.


PTH reversed the deleterious effects of long-term protein undernutrition on mechanical fixation and bone microarchitecture and improved implant osseointegration more than pamidronate or renutrition, likely through changes to structure model index.


Implants Nutrition Pamidronate Parathyroid hormone Rodents 



The authors thank S. Clément for expert animal care, diet preparations, and blood collection; Dr. A. Laib for technical help in using µCT; Dr. M. Cattani, I. Badoud and V. Chatelain for biomechanical testing; and M. Perez for secretarial assistance. This research project was supported by Swiss National Research Foundation (Grant 3200BO-100714).

Conflicts of interest



  1. 1.
    Smoliner C, Norman K, Scheufele R, Hartig W, Pirlich M, Lochs H (2008) Effects of food fortification on nutritional and functional status in frail elderly nursing home residents at risk of malnutrition. Nutrition 24:1139–1144CrossRefPubMedGoogle Scholar
  2. 2.
    Preben Ulrich P (2005) Nutritional care: the effectiveness of actively involving older patients. J Clin Nurs 14:247–255CrossRefGoogle Scholar
  3. 3.
    Guigoz YY, Lauque SS, Vellas BJBJ (2002) Identifying the elderly at risk for malnutrition. The mini nutritional assessment. Clin Geriatr Med 18:737–757CrossRefPubMedGoogle Scholar
  4. 4.
    Van Nes M-C, Herrmann FR, Gold G, Michel J-P, Rizzoli R (2001) Does the mini nutritional assessment predict hospitalization outcomes in older people? Age Ageing 30:221–226CrossRefPubMedGoogle Scholar
  5. 5.
    Feldblum I, German L, Castel H, Harman-Boehm I, Bilenko N, Eisinger M, Fraser D, Shahar D (2007) Characteristics of undernourished older medical patients and the identification of predictors for undernutrition status. J Nutr 6:37CrossRefGoogle Scholar
  6. 6.
    Rizzoli R, Ammann P, Bourrin S, Chevalley T, Bonjour JP (2001) Protein intake and bone homeostasis. In: Burckhardt P, Dawson-Hughes B, Heaney RP (eds) Nutritional aspects of osteoporisis. Academic, San Diego, pp 219–235Google Scholar
  7. 7.
    Omran ML, Morley JE (2000) Assessment of protein energy malnutrition in older persons, part I: history, examination, body composition, and screening tools. Nutrition 16:50–63CrossRefPubMedGoogle Scholar
  8. 8.
    Omran ML, Morley JE (2000) Assessment of protein energy malnutrition in older persons, part II: laboratory evaluation. Nutrition 16:131–140CrossRefPubMedGoogle Scholar
  9. 9.
    Soini H, Routasalo P, Lagstrom H (2004) Characteristics of the mini-nutritional assessment in elderly home-care patients. Eur J Clin Nutr 58:64–70CrossRefPubMedGoogle Scholar
  10. 10.
    Edington J, Boorman J, Durrant ER, Perkins A, Giffin CV, James R, Thomson JM, Oldroyd JC, Smith JC, Torrance AD, Blackshaw V, Green S, Hill CJ, Berry C, McKenzie C, Vicca N, Ward JE, Coles SJ (2000) Prevalence of malnutrition on admission to four hospitals in England. Clin Nutr 19:191–195CrossRefPubMedGoogle Scholar
  11. 11.
    Chandra RK (1997) Nutrition and the immune system: an introduction. Am J Clin Nutr 66:460S–463SPubMedGoogle Scholar
  12. 12.
    Paillaud E, Herbaud S, Caillet P, Lejonc J-L, Campillo B, Bories P-N (2005) Relations between undernutrition and nosocomial infections in elderly patients. Age Ageing 34:619–625CrossRefPubMedGoogle Scholar
  13. 13.
    Wintergerst ES, Maggini S, Hornig DH (2007) Contribution of selected vitamins and trace elements to immune function. Ann Nutr Metab 51:301–323CrossRefPubMedGoogle Scholar
  14. 14.
    Rizzoli R (2008) Nutrition: its role in bone health. Best Pract Res Clin Endocrinol Metab 22:813–829CrossRefPubMedGoogle Scholar
  15. 15.
    Bruyere O, Brandi ML, Burlet N, Harvey N, Lyritis G, Minne H, Boonen S, Reginster JY, Rizzoli R, Akesson K (2008) Post-fracture management of patients with hip fracture: a perspective. Curr Med Res Opin 24:2841–2851CrossRefPubMedGoogle Scholar
  16. 16.
    Roubenoff RR (2000) Sarcopenia and its implications for the elderly. Eur J Clin Nutr 54(Suppl 3):S40–S47PubMedGoogle Scholar
  17. 17.
    Gherini S, Vaughn BK, Lombardi AV Jr, Mallory TH (1993) Delayed wound healing and nutritional deficiencies after total hip arthroplasty. Clin Orthop 293:188–195PubMedGoogle Scholar
  18. 18.
    Greene KA, Wilde AH, Stulberg BN (1991) Preoperative nutritional status of total joint patients. Relationship to postoperative wound complications. J Arthroplast 6:321–325CrossRefGoogle Scholar
  19. 19.
    Marin LA, Salido JA, Lopez A, Silva A (2002) Preoperative nutritional evaluation as a prognostic tool for wound healing. Acta Orthop Scand 73:2–5PubMedGoogle Scholar
  20. 20.
    Rai J, Gill SS, Kumar BR (2002) The influence of preoperative nutritional status in wound healing after replacement arthroplasty. Orthopedics 25:417–421PubMedGoogle Scholar
  21. 21.
    Dayer R, Rizzoli R, Kaelin A, Ammann P (2006) Low protein intake is associated with impaired titanium implant osseointegration. J Bone Miner Res 21:258–264CrossRefPubMedGoogle Scholar
  22. 22.
    Aleksyniene R, Hvid I (2004) Parathyroid hormone—possible future drug for orthopedic surgery. Medicina (Kaunas) 40:842–849Google Scholar
  23. 23.
    Skripitz R, Aspenberg P (2004) Parathyroid hormone—a drug for orthopedic surgery? Acta Orthop Scand 75:654–662PubMedCrossRefGoogle Scholar
  24. 24.
    Shanbhag AS (2006) Use of bisphosphonates to improve the durability of total joint replacements. J Am Acad Orthop Surg 14:215–225PubMedGoogle Scholar
  25. 25.
    Tokugawa Y, Shirota T, Ohno K, Yamaguchi A (2003) Effects of bisphosphonate on bone reaction after placement of titanium implants in tibiae of ovariectomized rats. Int J Oral Maxillofac Implants 18:66–74PubMedGoogle Scholar
  26. 26.
    Narai S, Nagahata S (2003) Effects of alendronate on the removal torque of implants in rats with induced osteoporosis. Int J Oral Maxillofac Implants 18:218–223PubMedGoogle Scholar
  27. 27.
    Skoglund B, Holmertz J, Aspenberg P (2004) Systemic and local ibandronate enhance screw fixation. J Orthop Res 22:1108–1113CrossRefPubMedGoogle Scholar
  28. 28.
    Astrand J, Aspenberg P (2004) Topical, single dose bisphosphonate treatment reduced bone resorption in a rat model for prosthetic loosening. J Orthop Res 22:244–249CrossRefPubMedGoogle Scholar
  29. 29.
    Soininvaara TA, Jurvelin JS, Miettinen HJ, Suomalainen OT, Alhava EM, Kroger PJ (2002) Effect of alendronate on periprosthetic bone loss after total knee arthroplasty: a one-year, randomized, controlled trial of 19 patients. Calcif Tissue Int 71:472–477CrossRefPubMedGoogle Scholar
  30. 30.
    Wilkinson JM, Stockley I, Peel NF, Hamer AJ, Elson RA, Barrington NA, Eastell R (2001) Effect of pamidronate in preventing local bone loss after total hip arthroplasty: a randomized, double-blind, controlled trial. J Bone Miner Res 16:556–564CrossRefPubMedGoogle Scholar
  31. 31.
    Skripitz R, Aspenberg P (2001) Early effect of parathyroid hormone (1–34) on implant fixation. Clin Orthop Relat Res 392:427–432CrossRefPubMedGoogle Scholar
  32. 32.
    Shirota T, Tashiro M, Ohno K, Yamaguchi A (2003) Effect of intermittent parathyroid hormone (1-34) treatment on the bone response after placement of titanium implants into the tibia of ovariectomized rats. J Oral Maxillofac Surg 61:471–480CrossRefPubMedGoogle Scholar
  33. 33.
    Dayer R, Badoud I, Rizzoli R, Ammann P (2007) Defective implant osseointegration under protein undernutrition: prevention by PTH or pamidronate. J Bone Miner Res 22(10):1526–1533CrossRefPubMedGoogle Scholar
  34. 34.
    Ammann P, Bourrin S, Bonjour JP, Meyer JM, Rizzoli R (2000) Protein undernutrition-induced bone loss is associated with decreased IGF-I levels and estrogen deficiency. J Bone Miner Res 15:683–690CrossRefPubMedGoogle Scholar
  35. 35.
    Bourrin S, Toromanoff A, Ammann P, Bonjour JP, Rizzoli R (2000) Dietary protein deficiency induces osteoporosis in aged male rats. J Bone Miner Res 15:1555–1563CrossRefPubMedGoogle Scholar
  36. 36.
    Delmi M, Rapin CH, Bengoa JM, Delmas PD, Vasey H, Bonjour JP (1990) Dietary supplementation in elderly patients with fractured neck of the femur. Lancet 335:1013–1016CrossRefPubMedGoogle Scholar
  37. 37.
    Rizzoli R, Ammann P, Chevalley T, Bonjour JP (2001) Protein intake and bone disorders in the elderly. Jt Bone Spine 68:383–392CrossRefGoogle Scholar
  38. 38.
    Ammann P, Gasser JA, Rizzoli R (2003) Protein intake determines net bone strength response to PTh or GH, two anabolic agents increasing bone turnover. J Bone Miner Res 2:S386Google Scholar
  39. 39.
    Mekraldi S, Toromanoff A, Rizzoli R, Ammann P (2005) Pamidronate prevents bone loss and decreased bone strength in adult female and male rats fed an isocaloric low-protein diet. J Bone Miner Res 20:1365–1371CrossRefPubMedGoogle Scholar
  40. 40.
    Butz F, Ogawa T, Chang TL, Nishimura I (2006) Three-dimensional bone-implant integration profiling using micro-computed tomography. Int J Oral Maxillofac Implants 21:687–695PubMedGoogle Scholar
  41. 41.
    Rebaudi A, Koller B, Laib A, Trisi P (2004) Microcomputed tomographic analysis of the peri-implant bone. Int J Periodontics Restor Dent 24:316–325Google Scholar
  42. 42.
    Ammann P, Laib A, Bonjour JP, Meyer JM, Ruegsegger P, Rizzoli R (2002) Dietary essential amino acid supplements increase bone strength by influencing bone mass and bone microarchitecture in ovariectomized adult rats fed an isocaloric low-protein diet. J Bone Miner Res 17:1264–1272CrossRefPubMedGoogle Scholar
  43. 43.
    Ito M, Nishida A, Koga A, Ikeda S, Shiraishi A, Uetani M, Hayashi K, Nakamura T (2002) Contribution of trabecular and cortical components to the mechanical properties of bone and their regulating parameters. Bone 31:351–358CrossRefPubMedGoogle Scholar
  44. 44.
    Wronski TJ, Pun S, Liang H (1999) Effects of age, estrogen depletion, and parathyroid hormone treatment on vertebral cancellous wall width in female rats. Bone 25:465–468CrossRefPubMedGoogle Scholar
  45. 45.
    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 18:1932–1941CrossRefPubMedGoogle Scholar
  46. 46.
    Schurch M-A, Rizzoli R, Slosman D, Vadas L, Vergnaud P, Bonjour J-P (1998) Protein supplements increase serum insulin-like growth factor-i levels and attenuate proximal femur bone loss in patients with recent hip fracture: a randomized, double-blind, placebo-controlled trial. Ann Intern Med 128:801–809PubMedGoogle Scholar
  47. 47.
    Geinoz G, Rapin CH, Rizzoli R, Kraemer R, Buchs B, Slosman D, Michel JP, Bonjour JP (1993) Relationship between bone mineral density and dietary intakes in the elderly. Osteoporos Int 3:242–248CrossRefPubMedGoogle Scholar
  48. 48.
    Gaillard C, Alix E, Boirie Y, Berrut G, Ritz P (2008) Are elderly hospitalized patients getting enough protein? J Am Geriatr Soc 56:1045–1049CrossRefPubMedGoogle Scholar
  49. 49.
    Wong S, Lau EM, Lau WW, Lynn HS (2004) Is dietary counselling effective in increasing dietary calcium, protein and energy intake in patients with osteoporotic fractures? A randomized controlled clinical trial. J Hum Nutr Diet 17:359–364CrossRefPubMedGoogle Scholar
  50. 50.
    Kasaoka S, Oh-hashi A, Morita T, Kiriyama S (1999) Nutritional characterization of millet protein concentrates produced by a heat-stable [alpha]-amylase digestion. Nutr Res 19:899–910CrossRefGoogle Scholar
  51. 51.
    Carinci F, Volinia S, Pezzetti F, Francioso F, Tosi L, Piattelli A (2003) Titanium-cell interaction: analysis of gene expression profiling. J Biomed Mater Res B Appl Biomater 66:341–346CrossRefPubMedGoogle Scholar
  52. 52.
    Taylor JC, Cuff SE, Leger JP, Morra A, Anderson GI (2002) In vitro osteoclast resorption of bone substitute biomaterials used for implant site augmentation: a pilot study. Int J Oral Maxillofac Implants 17:321–330PubMedGoogle Scholar
  53. 53.
    Weiss P, Obadia L, Magne D, Bourges X, Rau C, Weitkamp T, Khairoun I, Bouler JM, Chappard D, Gauthier O, Daculsi G (2003) Synchrotron X-ray microtomography (on a micron scale) provides three-dimensional imaging representation of bone ingrowth in calcium phosphate biomaterials. Biomaterials 24:4591–4601CrossRefPubMedGoogle Scholar
  54. 54.
    Musey VC, Goldstein S, Farmer PK, Moore PB, Phillips LS (1993) Differential regulation of IGF-1 and IGF-binding protein-1 by dietary composition in humans. Am J Med Sci 305:131–138CrossRefPubMedGoogle Scholar
  55. 55.
    Jensen JE, Jensen TG, Smith TK, Johnston DA, Dudrick SJ (1982) Nutrition in orthopaedic surgery. J Bone Joint Surg Am 64:1263–1272PubMedGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2009

Authors and Affiliations

  • R. Dayer
    • 1
  • T. C. Brennan
    • 1
  • R. Rizzoli
    • 1
  • P. Ammann
    • 1
  1. 1.Division of Bone Diseases (WHO Collaborating Center for Osteoporosis Prevention), Department of Rehabilitation and GeriatricsGeneva University Hospitals and Faculty of MedicineGeneva 14Switzerland

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