Journal of Endocrinological Investigation

, Volume 28, Issue 5, pp 202–208 | Cite as

Effects of neridronate treatment in elderly women with osteoporosis

  • T. Cascella
  • T. Musella
  • F. OrioJr
  • S. Palomba
  • G. Bifulco
  • C. Nappi
  • G. Lombardi
  • A. Colao
  • L. Tauchmanova
Original Articles


Osteoporosis is a common disorder, especially among elderly post-menopausal women. Elderly women are often affected by co-morbidities, impaired gastrointestinal function and reduced mobility; therefore, the treatment strategy for their osteoporosis can be difficult. In this randomized pilot study, we have investigated the effects of a 12-month treatment with neridronate on bone mineral density (BMD), bone turnover markers and quality of life (QoL). The study included 40 women (age, 65–80 yr; post-menopausal period, >15yr) from a single osteoporosis centre. Twenty women received a monthly im injection of 25 mg of neridronate associated with a daily dose of 500 mg of calcium and 400 U of vitamin D. Twenty women received calcium plus vitamin D supplements alone. Changes in BMD at the lumbar spine and femoral neck were measured by dual energy X-ray absorptiometry. Serum type I collagen C-telopeptide (sCTX), urinary free-deox-ypyridinoline (ufDPD), bone alkaline phosphatase (ALP) and serum osteocalcin levels were determined. For the QoL assessment, the Italian version of the SF-36 test was administrated. Spine and hip BMD rose by 6.6±3 and 4.2±2.3%, respectively (p<0.05), after 12 months of neridronate treatment. Markers of skeletal turnover significantly fell already after 3 months of neridronate treatment and decreased progressively thereafter within 12 months. The mean decrease at 12 months ranged from 38±11% for sCTX to 25.2±15% for ufDPD (p<0.001, all). The mean improvement in QoL in the treated group was 45.7% for bodily pain, 37.5% for general health perception, 23.1% for vitality, 18% for emotional role functioning and 12% for physical role functioning. The changes observed in BMD, turnover markers and QoL in the untreated group were ns. The intermittent neridronate administration was easily manageable and well tolerated. In conclusion, neridronate currently represents a valid option for the treatment of osteoporosis, since it helps just as much as oral BPs in the improvement of BMD and in particular conditions it can be even more effective.


Neridronate osteoporosis bone mineral density elderly women bone turnover 


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  1. 1.
    Black DM, Cummings SR, Karpf DB, et al. Randomised trial of effect of alendronate on risk of fracture in women existing vertebral fractures. Fracture Intervention Trial Research Group. Lancet 1996, 348: 1535–41.PubMedCrossRefGoogle Scholar
  2. 2.
    Harris ST, Watts NB, Genant HK, et al. Effects of risedronate treatment on vertebral and non-vertebral fractures in women with postmenopausal osteoporosis. A randomized controlled trial. Vertebral Efficacy With Risedronate Therapy (VERT) Study Group. JAMA 1999, 282: 1344–52.PubMedCrossRefGoogle Scholar
  3. 3.
    Cranney A, Guyatt G, Griffith L, et al. Meta-analyses of therapies for postmenopausal osteoporosis. IX: Summary of meta-analyses of therapies for postmenopausal osteoporosis. Endocr Rev 2002, 23: 570–8.PubMedCrossRefGoogle Scholar
  4. 4.
    Marcus R, Wong M, Heath H III, Stock JL. Antiresorptive treatment of postmenopausal osteoporosis: comparison of study designs and outcomes in large clinical trials with fracture as endpoint. Endocr Rev 2002, 23: 16–37.PubMedCrossRefGoogle Scholar
  5. 5.
    Fleisch H. Bisphosphonates — mechanism of action. Endocr Rev 1998, 19: 80–100.PubMedCrossRefGoogle Scholar
  6. 6.
    Okolicsanyi L, Dal Bo N. The gastrointestinal tolerability of bisphosphonates. Aging Clin Exp Res 2001, 13: 344–6.Google Scholar
  7. 7.
    Adami S., Zamberlan N. Adverse effects of bisphosphonates — a comparative review. Drug Saf, 1996, 14: 158–70.PubMedCrossRefGoogle Scholar
  8. 8.
    Adami S, Bhalla AK, Dorizzi R, Montesanti F, Rosini S, Salvagno G, Lo Cascio V. The acute-phase response after bisphosphonate administration. Calcif Tissue Int 1987, 41: 326–31.PubMedCrossRefGoogle Scholar
  9. 9.
    McCloskey EV, Yates AJ, Beneton MN, Galloway J, Harris S, Kanis JA. Comparative effects of intravenous bisphosphonates on calcium and skeletal metabolism in man. Bone 1987, 8 (Suppl 1): S35–41.PubMedGoogle Scholar
  10. 10.
    Reid IR, Brown JP, Burckhardt P, et al. Intravenous zoledronic acid in postmenopausal women with low bone mineral density. N Engl J Med 2002, 346: 653–61.PubMedCrossRefGoogle Scholar
  11. 11.
    Thiébaud D, Burckardt P, Kriegbaum H, et al. Three monthly intravenous injections of ibandronate in the treatment of postmenopausal osteoporosis, Am J Med 1997, 103: 297–8.CrossRefGoogle Scholar
  12. 12.
    Ringe JD, Dorst A, Faber H, Ibach K, Sorenson F. Intermittent intravenous ibandronate injections reduce vertebral fracture risk in corticosteroid-induced osteoporosis: results from a long-term comparative study. Osteoporosis Int 2003, 14: 801–7.CrossRefGoogle Scholar
  13. 13.
    Reid IR, Wattie DJ, Evans MC, Gamble GD, Stapleton JP, Cornish J. Continuous therapy with pamidronate, a potent bisphosphonate, in post-menopausal osteoporosis. J Clin Endocrinol Metab 1994, 79: 1595–9.PubMedGoogle Scholar
  14. 14.
    Gatti D, Adami S. New bisphosphonates in the treatment of bone diseases. Drugs Aging 1999, 15: 285–96.PubMedCrossRefGoogle Scholar
  15. 15.
    Widler L, Jaeggi KA, Glatt M, et al. Highly potent geminal bisphosphonates. From pamidronate disodium (Aredia) to zoledronic acid (Zometa). J Med Chem 2002, 45: 3721–38.PubMedCrossRefGoogle Scholar
  16. 16.
    Frediani B, Spreafico A, Capperucci C, et al. Long-term effects of neridronate on human osteoblastic cell cultures. Bone 2004, 35: 859–69.PubMedCrossRefGoogle Scholar
  17. 17.
    Adami S, Gatti D, Colapietro F, et al. Intravenous neridronate in adults with osteogenesis imperfecta. J Bone Miner Res 2003, 18: 126–30.PubMedCrossRefGoogle Scholar
  18. 18.
    Atkins RM, Yates AJ, Gray RE, et al. “Aminohexane diphosphonates in the treatment of Paget’s disease of bone”. J Bone Miner Res 1987, 2: 273–9.PubMedCrossRefGoogle Scholar
  19. 19.
    Delmas PD, Chapuy MC, Edouard C, Meunier PJ. Beneficial effects of aminohexane diphosphonate in patients with Paget’s disease of bone resistant to sodium etidronate. Am J Med 1987, 83: 276–82.PubMedCrossRefGoogle Scholar
  20. 20.
    Adami S, Bevilacqua M, Broggini M, et al. Short-term intravenous therapy with neridronate in Paget’s disease. Clin Exp Rheumatol 2002, 20: 55–8.PubMedGoogle Scholar
  21. 21.
    O’Rourke NP, McCloskey EV, Rosini S, Coleman RE, Kanis JA. Treatment of malignant hypercalcemia with aminohexane bisphosphonate (neridronate). Br J Cancer 1994, 69: 914–7.PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Morabito N, Gaudio A, Lasco A, et al. Neridronate prevents bone loss in patients receiving androgen deprivation therapy for prostate cancer. J Bone Miner Res 2004, 19: 1766–70.PubMedCrossRefGoogle Scholar
  23. 23.
    Tobias JH, Laversuch CJ, Chambers TJ, Gallagher AC. Aminohexane bisphosphonate suppress bone turnover in postmenopausal women more rapidly than oestrogen-gestagen therapy. Br J Rheumatol 1996, 35: 636–41.PubMedCrossRefGoogle Scholar
  24. 24.
    Braga V, Gatti D, Colapietro F, et al. Intravenous neridronate in the treatment of postmenopausal osteoporosis. Bone 2003, 33: 342–5.PubMedCrossRefGoogle Scholar
  25. 25.
    World Health Organization Study Group. (1994) Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. WHO Technical Report Series 843. WHO, Geneve.Google Scholar
  26. 26.
    Minne HW, Leidig G, Wüster C, et al. A newly defined spine deformity index (SDI) to quantitative vertebral crush fractures in patients with osteoporosis. Bone Miner 1988, 3: 335–49.PubMedGoogle Scholar
  27. 27.
    Ware JE Jr, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care 1992, 30: 473–83.PubMedCrossRefGoogle Scholar
  28. 28.
    Ware JE, Snow KK, Kosinski M, Gandek B. SF-36 Health Survey Manual and Interpretation Guide. The Health Institute, New England Medical Centre, Boston. 1993.Google Scholar
  29. 29.
    Apolone G, Mosconi P. The Italian SF-36 health survey: translation, validation and norming. J Clin Epidemiol 1998, 51: 1025–36.PubMedCrossRefGoogle Scholar
  30. 30.
    American Psychiatric Association. Diagnostic and Statistical Manual of Mental disorders. 4thed. Washington: American Psychiatric Association, DC. 1994.Google Scholar
  31. 31.
    Spitzer RL, Williams JBW, Gibbon M, Willams JBM. Structured Clinical Interview for DSM-IV Axis I Disorders (SCID), Clinician Version: User’s Guide. Washington: American Psychiatric Association Press, DC. 1996.Google Scholar
  32. 32.
    Glorieux FH, Bishop NJ, Plotkin H, Chabot G, Lanoue G, Travers R. Cyclic administration of pamidronate in children with severe osteogenesis imperfecta. N Engl J Med 1998, 339: 947–52.PubMedCrossRefGoogle Scholar
  33. 33.
    Tauchmanovà L, Ricci P, Serio B, et al. Effect of intravenous zoledronic acid administration in patients with low bone mineral density and/or fast bone loss after allogeneic stem cell transplantation. J Clin Endocrinol Metab 2005, 90:627–34.PubMedCrossRefGoogle Scholar
  34. 34.
    Passeri M, Baroni MC, Pedrazzoni M, et al. Intermittent treatment with intravenous 4-amino-1-hydroxybutylidene-1, 1 -bisphosphonate (AHBuBP) in the therapy of postmenopausal osteoporosis. Bone Miner Res 1991, 15: 237–48.CrossRefGoogle Scholar
  35. 35.
    Sartori L, Adami S, Filipponi P, Crepaldi G. Injectable bisphosphonates in the treatment of postmenopausal osteoporosis. Aging Clin Exp Res 2003, 15: 271–83.PubMedCrossRefGoogle Scholar
  36. 36.
    Ravn P, Clemmesen B, Riis BJ, Christiansen C. The effect on bone mass and bone markers of different doses of Ibandronate: a new bisphosphonate for prevention and treatment of postmenopausal osteoporosis: a 1-year, randomized, double-blind, placebo-controlled dose-finding study. Bone 1996, 19: 527–33.PubMedCrossRefGoogle Scholar
  37. 37.
    Pecherstofer M, Ludwig H, Schlosser K, Buck S, Huss HJ, Body JJ. Administration of the bisphosphonate Ibandronato (BM 21.0955) by intravenous bolo injection. J Bone Miner Res 1996, 11: 587–93.CrossRefGoogle Scholar
  38. 38.
    Fromigue O, Body JJ. Bisphosphonates influence the proliferation and the maturation of normal human osteoblasts. J Endocrinol Invest 2002, 25: 539–46.PubMedCrossRefGoogle Scholar
  39. 39.
    Giuliani N, Pedrazzoni M, Negri G, Passeri G, Impicciatore M, Girasole G. Bisphosphonates stimulate formation of osteoblast precursors and mineralized nodules in murine and human bone marrow cultures in vitro and promote early osteoblastogenesis in young and aged mice in vivo. Bone 1998, 22: 455–61.PubMedCrossRefGoogle Scholar
  40. 40.
    Plotkin LI, Weinstein RS, Parfitt AM, Roberson PK, Manolagas SC, Bellido T. Prevention of osteocyte and osteoblast apoptosis by bisphosphonates and calcitonin. J Clin Invest 1999, 104: 1363–74.PubMedCentralPubMedCrossRefGoogle Scholar
  41. 41.
    Marshall D, Johnell O, Wedell H. Meta analysis of how well measures of bone mineral density predict occurrence of osteoporotic fracture. BMJ 1996, 312: 1254–9.PubMedCentralPubMedCrossRefGoogle Scholar
  42. 42.
    Cranney A, Welch V, Tugwell P, et al. Responsiveness of endpoints in osteoporosis clinical trials- an update. J Rheumatol 1999, 26: 222–8.PubMedGoogle Scholar
  43. 43.
    Wasnich RD, Miller PD. Antifracture efficacy of antiresorptive agents are related to changes in bone density. J Clin Endocrinol Metab 2000, 85: 231–6.PubMedCrossRefGoogle Scholar
  44. 44.
    Cummings SR, Nevitt MC, Browner WS, et al. Risk factors for hip fracture in white women. N Engl J Med 1995, 338: 736–46.Google Scholar
  45. 45.
    Turner CH. Yield behaviour of cancellous bone. J Biomech Eng 1989, 111: 1–5.CrossRefGoogle Scholar
  46. 46.
    Filipponi P, Cristallini S, Policani G, Schifini MF, Casciari C, Garinei P. Intermittent versus continous clodronate administration in postmenopausal women with low bone mass. Bone 2000, 26: 268–74.CrossRefGoogle Scholar
  47. 47.
    Rossini M, Braga V, Gatti D, Gerardi D, Zamberlan N, Adami S. Intramuscular clodronate therapy in postmenopausal osteoporosis. Bone 1999, 24: 125–9.PubMedCrossRefGoogle Scholar
  48. 48.
    Gnudi S, Lisi L, Fini M, Malavoglia N. Effect of intramuscular clodronate on bone mass and metabolism in osteoporotic women. Int J Tissue React 2001, 23: 33–7.PubMedGoogle Scholar
  49. 49.
    Schweitzer DH, Oostendorp-van de Ruit M, Van der Pluijm G, Lowik CW, Papapoulos SE. Interleukin-6 and the acute phase response during treatment of patients with Paget’s disease with the nitrogen-containing bisphosphonate dimethylaminohydroxypro-pylidene bisphosphonate. J Bone Miner Res 1991, 10: 956–62.CrossRefGoogle Scholar
  50. 50.
    La Montagna G, Malesci D, Tirri R, Valentini G. Successful neridronate therapy in transient osteoporosis of the hip. Clin Rheumatol 2005, 24: 67–9.PubMedCrossRefGoogle Scholar

Copyright information

© Italian Society of Endocrinology (SIE) 2005

Authors and Affiliations

  • T. Cascella
    • 1
  • T. Musella
    • 1
  • F. OrioJr
    • 1
  • S. Palomba
    • 2
  • G. Bifulco
    • 3
  • C. Nappi
    • 3
  • G. Lombardi
    • 1
  • A. Colao
    • 1
  • L. Tauchmanova
    • 1
  1. 1.Department of Molecular and Clinical Endocrinology and OncologyUniversity “Federico II” of NaplesItaly
  2. 2.Department of GynecologyUniversity of Catanzaro “Magna Graecia”CatanzaroItaly
  3. 3.Department of GynecologyUniversity “Federico II” of NaplesNaples

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