Zoledronic acid: Clinical utility and patient considerations in osteoporosis and low bone mass

Drug Design, Development and Therapy

Volumn 4, Issue , 2010, Pages 321-335

  Hamdy, Ronald C ^a,b  

^a East Tennessee State University   (United States)

^b Mountain Home Veterans Administration   (United States)

Author keywords

Bisphosphonates; Osteopenia; Osteoporosis; Zoledronate; Zoledronic acid

Indexed keywords

ALENDRONIC ACID; ANTIESTROGEN; AROMATASE INHIBITOR; BISPHOSPHONIC ACID DERIVATIVE; CREATININE; GLUCOCORTICOID; PLACEBO; RISEDRONIC ACID; TAMOXIFEN; ZOLEDRONIC ACID; BONE DENSITY CONSERVATION AGENT; IMIDAZOLE DERIVATIVE;

ANDROGEN DEPRIVATION THERAPY; ARTHRALGIA; ASYMPTOMATIC DISEASE; BONE DENSITY; BONE MASS; BONE PAIN; BREAST CANCER; CONJUNCTIVITIS; CORTICOSTEROID INDUCED OSTEOPOROSIS; COST EFFECTIVENESS ANALYSIS; DISEASE ASSOCIATION; DISEASE SEVERITY; DOSE RESPONSE; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG CONTRAINDICATION; DRUG COST; DRUG DISTRIBUTION; DRUG EFFICACY; DRUG FATALITY; DRUG HALF LIFE; DRUG INDICATION; DRUG MECHANISM; DRUG STRUCTURE; DRUG URINE LEVEL; EYE INFLAMMATION; EYE PAIN; FATIGUE; FEMUR FRACTURE; FEVER; GASTROINTESTINAL SYMPTOM; HEALTH CARE NEED; HEART ARRHYTHMIA; HEART ATRIUM FIBRILLATION; HIP FRACTURE; HUMAN; HYPOCALCEMIA; HYPOTHYROIDISM; JAW OSTEONECROSIS; MALAISE; MUSCULOSKELETAL PAIN; NEPHROTOXICITY; OSTEOLYSIS; OSTEOPENIA; OSTEOPOROSIS; OUTCOME ASSESSMENT; PATIENT COMPLIANCE; PHOTOPHOBIA; POSTMENOPAUSE OSTEOPOROSIS; PROSTATE CANCER; REVIEW; RISK ASSESSMENT; RISK FACTOR; SCLERITIS; SEX RATIO; SIDE EFFECT; TREATMENT PLANNING; UVEITIS; VISUAL IMPAIRMENT; VITAMIN D DEFICIENCY; WEAKNESS; DRUG ADMINISTRATION; DRUG EFFECT; FEMALE; KIDNEY; MALE; METABOLISM;

BONE DENSITY; BONE DENSITY CONSERVATION AGENTS; DIPHOSPHONATES; DRUG ADMINISTRATION SCHEDULE; FEMALE; HUMANS; HYPOCALCEMIA; IMIDAZOLES; KIDNEY; MALE; OSTEOPOROSIS; PATIENT COMPLIANCE;

EID: 79952464694     PISSN: 11778881     EISSN: None     Source Type: Journal    
DOI: 10.2147/DDDT.S6287     Document Type: Review

References (103)

1. Cummings SR, Melton LJ. Epidemiology and outcomes of osteoporotic fractures. Lancet. 2002;359:1761-1767.
2. Consensus Development Conference 1991. Prophylaxis and treatment of osteoporosis. Am J Med. 1991;90:107-110.
3. NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy. JAMA. 2001;285:785-795.
4. Riggs BL, Melton LJ III. The worldwide problem of osteoporosis: Insights afforded by epidemiology. Bone. 1995;17 Suppl 5:S505-S511.
5. Burge RT, Dawson-Hughes B, Solomon D, et al. Incidence and economic burden of osteoporotic fractures in the United States, 2005-2025. J Bone Miner Res. 2007;34:465-475.
6. WHO Scientific Group on the Assessment of Osteoporosis at the Primary Health Care Level. Summary meeting report. Proceedings of the World Health Organization Meeting 5-7 May 2004, Brussels, Belgium. Available from: http://www.who.int/chp/topics/Osteoporosis. pdf. Accessed March 7, 2010.
7. World Health Organization Collaborating Centre for Metabolic Bone Diseases. FRAX® WHO fracture risk assessment tool. Available from: http://www.shef.ac.uk/FRAX®/tool.jsp?locationValue=9. Accessed March 7, 2010.
8. National Osteoporosis Foundation. Clinician's Guide to Prevention and Treatment of Osteoporosis. Washington DC: National Osteoporosis Foundation; 2010. Available from: www.nof.org/physguide. Accessed March 7, 2010.
9. American Orthopaedic Association. Own the Bone.™ Rosemont, IL: American Orthopaedic Association. Available from: http://www. ownthebone.org/providers. Accessed March 7, 2010.
10. Carmona R, Adachi R. Treatment of postmenopausal osteoporosis, patient perspectives - focus on once yearly zoledronic acid. Patient Pref Adherence. 2009;3:189-193.
11. Lewiecki EM. A clinician's perspective on the use of zoledronic acid in the treatment postmenopausal osteoporosis. J Clin Densitom. 2008;11: 478-484.
12. Siris ES, Selby POL, Saag KG, et al. Impact of osteoporosis treatment adherence on fracture rates in North America and Europe. Am J Med. 2009;122(Suppl 2A):S3-S13.
13. US Department of Health and Human Services. Bone health and osteoporosis: A report of the Surgeon General. US Department of Health and Human Services, Office of the Surgeon Gene r a l, Rockvi l l e, MD [upda t ed 2004 Oc tobe r 14]. Available from: http://www.surgeongeneral.gov/library/bonehealth/. Accessed March 7, 2010.
14. McClung M, Recker R, Miller P, et al. Intravenous zoledronic acid 5 mg in the treatment of postmenopausal women with low bone density previously treated with alendronate. Bone. 2007;41: 122-128.
15. Deeks ED, Perry CM. Zoledronic acid: A review of its use in the treatment of osteoporosis. Drugs Aging. 2008;25:963-986.
16. Demontiero O, Duque G. Once-yearly zoledronic acid in hip fracture prevention. Clin Interv Aging. 2009;4:153-164.
17. Cole RE, Harris T. Preventing nonvertebral osteoporotic fractures with extended-interval bisphosphonates: Regimen selection and clinical application. Medscape J Med. 2009 [serial online];11:12. Available from: http://search.medscape.com/medscape-search?queryText=preventing% 20nonvertebral. Accessed March 7, 2010.
18. Fardellone P, Cortet B, Legrand E, et al. Cost-effectiveness model of using zoledronic acid once a year versus current treatment strategies in postmenopausal osteoporosis. Joint Bone Spine. 2010;77: 53-57.
19. Perazella MA, Markowtiz GS. Bisphosphonate nephrotoxicity. Kidney Int. 2008;74:1385-1393.
20. Reclast [Package insert]. Novartis Pharmaceuticals, East Hanover, NJ; May 2009. http://www.pharma.us.novartis.com/product/pi/pdf/reclast. pdf. Accessed March 7, 2010.
21. Lambrinoudaki I, Vlachou S, Galapi F, et al. Once-yearly zoledronic acid in the prevention of osteoporotic bone fractures in postmenopausal women. Clin Interv Aging. 2008;3:445-451.
22. Kavanagh KL, Guo K, Dunford JE, et al. The molecular mechanism of nitrogen-containing bisphosphonates as antiosteoporosis drugs. Proc Natl Acad Sci U S A. 2006;103:7829-7834.
23. Delmas PD, Munoz F, Black DM, et al. Effects of yearly zoledronic acid 5 mg on bone turnover markers and relation of PINP with fracture reduction in postmenopausal women with osteoporosis. J Bone Miner Res. 2009;24:1544-1554.
24. Recker RR, Delmas PD, Halse J, et al. Effects of intravenous zoledronic acid once yearly on bone remodeling and bone structure. J Bone Miner Res. 2008;23:6-16.
25. Black DM, Delmas PD, Eastell R, et al. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med. 2007;356: 1809-1822.
26. Boonen S, Black DM, Colon-Emeric CS, et al. Efficacy and safety of a once-yearly intravenous zoledronic acid 5 mg for fracture prevention in elderly postmenopausal women with osteoporosis aged 75 and older. J Amer Geriatr Soc. 2010;58:292-299.
27. MacLean C, Newberry S, Maglione M, et al. Systematic review: Comparative effectiveness of treatments to prevent fractures in men and women with low bone density or osteoporosis. Ann Intern Med. 2008;148:197-213.
28. Bilezikian JP. Efficacy of bisphosphonates in reducing fracture risk in postmenopausal osteoporosis. Am J Med. 2009;122(Suppl 2): S14-S21.
29. Reid DM, Devogelaer JP, Saag K, et al; HORIZON investigators. Zoledronic acid and risedronate in the prevention and treatment of glucocorticoid-induced osteoporosis (HORIZON): A multicenter, double-blind, double-dummy, randomized controlled trial. Lancet. 2009;373:1253-1263.
30. Lyles KW, Colon-Emeric CS, Magaziner JS, et al. Zoledronic acid and clinical fractures and mortality after hip fracture. N Engl J Med. 2007; 357:1799-1809.
31. Eriksen EF, Lyles KW, Colon-Emeric CS, et al. Antifracture efficacy and reduction of mortality in relation to timing of the first dose of zoledronic acid after hip fracture. J Bone Miner Res. 2009;24:1308-1313.
32. Compston J. Treatments for osteoporosis - looking beyond the HORIZON [Editorial]. N Engl J Med. 356;18:1878-1880.
33. Piper PK Jr, Gruntmanis U. Management of osteoporosis in the aging male: Focus on zoledronic acid. Clin Interv Aging. 2009;4:289-303.
34. Biannnual IV zoledronic acid (Reclast) for prevention of osteoporosis. The Medical Letter: On Drugs and Therapies. 2009;51(1315):49. Available from: www.medicalletter.org. Accessed March 7, 2010.
35. McClung M, Miller P, Recknor C, et al. Zoledronic acid for the prevention of bone loss in postmenopausal women with low bone mass. Obstet Gynecol. 2009;114:999-1007.
36. Brufsky AM. Zoledronic acid for cancer therapy-induced and postmenopausal bone loss. Expert Opin Pharmacother. 2008;9:1013-1028.
37. Doggrell SA. Clinical efficacy and safety of zoledronic acid in prostate and breast cancer. Expert Rev Anticancer Ther. 2009;9:1211-1218.
38. Polascik TJ, Mouraviev V. Zoledronic acid in the management of metastatic bone disease. Therap Clin Risk Manag. 2008;4:261-268.
39. Body JJ, Bergmann P, Boonen S, et al. Management of cancer treatment-induced bone loss in early breast and prostate cancer - a consensus paper of the Belgian Bone Club. Osteoporos Int. 2007;18: 1439-1450.
40. Brufsky AM, Bosserman LD, Caradonna RR, et al. Zoledronic acid effectively prevents aromatase inhibitor-associated bone loss in postmenopausal women with early breast cancer receiving adjuvant letrozole: Z-FAST Study 36-month follow-up results. Clin Breast Cancer. 2009;9:77-85.
41. Hines SL, Sloan JA, Atherton PJ, et al. Zoledronic acid for treatment of osteopenia and osteoporosis in women with primary breast cancer undergoing adjuvant aromatase inhibitor therapy. Breast. 2010;19:92-96.
42. Hershman DL, McMahon DJ, Crew KD, et al. Zoledronic acid prevents bone loss in premenopausal women undergoing adjuvant chemotherapy for early-stage breast cancer. J Clin Oncol. 2008;26:4739-4745.
43. Gnant M, Mlineritsch B, Luschin-Ebengreuth G, et al. Adjuvant endocrine therapy plus zoledronic acid in premenopausal women with early-stage breast cancer: 5-year follow-up of the ABCSG-12 bone mineral density substudy. Lancet Oncol. 2008;9: 840-849.
44. Bundred NJ, Campbell ID, Davidson N, et al. Effective inhibition of aromatase inhibitor-associated bone loss by zoledronic acid in postmenopausal women with early breast cancer receiving adjuvant letrozole: ZO-FAST Study results. Cancer. 2008;112: 1001-1010.
45. Bhoopalam N, Campbell SC, Moritz T, et al. Intravenous zoledronic acid to prevent osteoporosis in a veteran population with multiple risk factors for bone loss on androgen deprivation therapy. J Urol. 2009; 182: 2257-2264.
46. Israeli RS, Rosenberg SJ, Saltzstein DR, et al. The effect of zoledronic acid on bone mineral density in patients undergoing androgen deprivation therapy. Clin Genitourin Cancer. 2007;5: 271-277.
47. Michaelson MD, Kaufman DS, Lee H, et al. Randomized controlled trial of annual zoledronic acid to prevent gonadotropin-releasing hormone agonist-induced bone loss in men with prostate cancer. J Clin Oncol. 2007; 25:1038-1042.
48. Ryan CW, Huo D, Bylow K, et al. Suppression of bone density loss and bone turnover in patients with hormone-sensitive prostate cancer and receiving zoledronic acid. BJU Int. 2007;100:70-75.
49. Smith MR, Eastham J, Gleason DM, et al. Randomized controlled trial of zoledronic acid to prevent bone loss in men receiving androgen deprivation therapy for nonmetastatic prostate cancer. J Urol. 2003;170 (6 Pt 1):2392-2393.
50. Crawford BAL, Kam C, Pavlovic J, et al. Zoledronic acid prevents bone loss after liver transplantation: A randomized, double-blind, placebocontrolled trial. Ann Int Med. 2006;144:239-248.
51. Hamdy RC, Krishnaswamy G, Cancellaro V, et al. Changes in bone mineral content and density following strokes. Am J Phys Med Rehabil. 1993;72:188-191.
52. Hamdy RC, Moore SW, Cancellaro VA, et al. Long term effects of strokes on bone mass. Am J Phys Med Rehabil. 1995;74:351-356.
53. Poole KES, Loveridge N, Rose CM, et al. A single infusion of zoledronate prevents bone loss after stroke. Stroke. 2007;38:1519-1525.
54. Huang J, Meixner L, Fernandez S, et al. A double-blinded, randomized controlled trial of zoledronate therapy for HIV-associated osteopenia and osteoporosis. AIDS. 2009;23:51-57.
55. Berenson JR, Yellin O, Boccia RV, et al. Zoledronic acid markedly improves bone mineral density for patients with monoclonal gammopathy of undetermined significance and bone loss. Clin Cancer Res. 2008;14:6289-6295.
56. Otrock ZK, Azar ST, Shamseddeen WA, et al. Intravenous zoledronic acid treatment in thalassemia-induced osteoporosis; results of a phase II clinical trial. Ann Hematol. 2006;85:605-609.
57. Voskaridou E, Anagnostopoulous A, Konstantopoulous K, et al. Zoledronic acid for the treatment of osteoporosis in patients with beta-thalassemia: Results from a single-center, randomized, placebocontrolled trial. Haematologica. 2006;91:1193-1202.
58. Perifanis V, Vyzantiadis T, Tziomalos K, et al. Effect of zoledronic acid on markers of bone turnover and mineral density in osteoporotic patients with beta-thalassaemia. Ann Hematol. 2007;86:23-30.
59. Olson K, Van Poznak C. Significance and impact of bisphosphonate induced acute phase responses. J Oncol Pharm Pract. 2007;13: 223-229.
60. Papapetrou PD. Bisphosphonate-associated adverse events. Hormones. 2009;8:96-110.
61. Kennel KA, Drake MT. Adverse effects of bisphosphonates: Implications for osteoporosis management. Mayo Clin Proc. 2009;84:632-638.
62. Wysowski DK, Chang JT. Alendronate and risedronate: Reports of severe bone, joint and muscle pain. Arch Intern Med. 2005;165: 346-347.
63. US Food and Drug Administration. Bisphosphonates (marketed as Actonel, Actonel + Ca, Aredia, Boniva, Didronel, Fosamax, Fosamax + D, Reclast, Skelid, and Zometa). Available from: http://www.fda.medwatch/safety/2008/safety08.htm#Bisphosphonates. Accessed March 7, 2010.
64. de Torrente da la Jara G, Pecoud A, Favrat B. Musculoskeletal pain in female asylum seekers and hypovitaminosis D3. BMJ. 2004;329: 156-157.
65. Gwynne Jones DP, Savage RL, Highton J. Alendronate induced synovitis. J Rheumatol. 2008;35:537-538.
66. Werner de Castro GR, Neves FS, de Magalhaes Souza Fialho SC, et al. Flare-up of hand osteoarthritis caused by zoledronic acid infusion. Osteoporos Int. Nov 21, 2009. [Epub ahead of print].
67. Gerster JC. Acute polyarthritis related to once-weekly alendronate in a woman with osteoporosis. J Rheumatol. 2004;31:829-830.
68. Pazianas M, Compston J, Huang CL. Atrial fibrillation and bisphosphonate therapy. J Bone Miner Res. 2010;25:2-10.
69. Heckbert SR, Li G, Cummings SR, et al. Use of alendronate and risk of incident atrial fibrillation in women. Arch Intern Med. 2008;166: 826-831.
70. Recker RR, Lewiecki EM, Miller PD, et al. Safety of bisphosphonates in the treatment of osteoporosis. Am J Med. 2009;122(Suppl 2A): S22-S32.
71. US Food and Drug Administration. The FDA safety information and adverse event reporting program. Available at: www.fda.gov/medwatch/safety/2008/safety08.htm#bisphosphonates2. Accessed March 7, 2010.
72. Boonen S, Sellmeyer DE, Lippuner K, et al; for the HORIZON Pivotal Fracture Trial. Renal safety of annual zoledronic acid infusions in osteoporotic postmenopausal women. Kidney Int. 2008;74:641-648.
73. Odvina CV, Zerwekh JE, Rao ES, et al. Severely suppressed bone turnover: A potential complication of alendronate therapy. J Clin Endocrinol Metab. 2005;90:1294-1301.
74. Visekruma M, Wilson D, McKienan FE. Severely suppressed bone turnover and atypical skeletal fragility. J Clin Endocrinol Metab. 2008; 93:2948-2952.
75. Goh SK, Yang KY, Koh JS, et al. Subtrochanteric insufficiency fractures in patients on alendronate therapy: A caution. J Bone Joint Surg (Br). 2007;89:349-353.
76. Neviaser AS, Lane JM, Lenart BA, et al. Low energy femoral shaft fractures associated with alendronate use. J Orthop Trauma. 2008; 22:346-350.
77. Kwek EB, Gosh SK, Koh JS, et al. An emerging pattern of subtrochanteric stress fractures: A long term complication of alendronate therapy? Injury. 2008;39:231-234.
78. Silverman SL, Landesberg L. Osteonecrosis of the jaw and the role of bisphosphonates: A critical review. Am J Med. 2009;122 suppl 2A: S33-S45.
79. Edwards BJ, Hellstein JW, Jacobsen PL, et al; American Dental Association Council on Scientific Affairs. Dental management of patients receiving oral bisphosphonate therapy - expert panel recommendations. Available from: http://docs.google.com/viewer?a=v&q=cache:REeDi 89n3XkJ:flouridation.org/prof/resources/topics/topics_osteonecrosis_bisphosphonate_ report.pdf+dental+management+of+patients+receivin g+bisphosphonate+therapy&hl=en&gl=us&pid=bl&srcid=ADGEESjB bRbOksrGZtIqeGAgZP8Tad_tR9KwQb_YQa4wM0k1Bb1YuQB0z_ MAR-UKG9o2ZK5HfascML1GoPAQDCWYuwgmeG1iu5Cz- YRjZi1y0M292RY2VfpM1y3xuzH1uE2L_- vD36Fn&sig=AHIEtbTxi SSidA6ORxdjmiBtb6esNOa5RQ. Accessed March 7, 2010.
80. Khosla S, Burr D, Cauley J, et al; for the American Society for Bone and Mineral Research. Bisphosphonate-associated osteonecrosis of the jaw: Report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res. 2007;22:1479-1491.
81. Advisory Task Force on Bisphosphonate-Related Osteonecrosis of the Jaw, American Association of Oral and Maxillofacial Surgeons. American Association of Oral and Maxillofacial Surgeons position paper on bisphosphonate-related osteonecrosis of the jaws. J Oral Maxillofac Surg. 2007;65:369-376.
82. Demerjian N, Bolla G, Spreux A. Severe oral ulcerations induced by alendronate. Clin Rheumatol. 2000;18:349-350.
83. Krasagakis K, Kruger-Krasagakis S, Ioannidou D, Tosca A. Chronic erosive and ulcerative oral lesions casued by incorrect administration of alendronate. J Am Acad Dermatol. 2004;50:651-652.
84. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the use of alendronate. N Engl J Med. 1996;335:1016-1021.
85. Bauer DC, Black D, Ensrud K, et al. Upper gastro-intestinal tract safety profile of alendronate. The Fracture Intervention Trial. Arch Intern Med. 2000;160:517-525.
86. Marx RRE, Sawatari Y, Fortin M, Broumand V. Bisphosphonateinduced exposed bone of the jaws: Risk factors, recognition, prevention and treatment. J Oral Maxillofac Surg. 2005;63:1567-1575.
87. Kimmel DB. Mechanism of action, pharmacokinetic and pharmacodynamic profile, and clinical applications of nitrogen-containing bisphosphonates. J Dent Res. 2007;86:1022-1033.
88. Woo SB, Hellstein JW, Kalmar JR. Narrative [corrected] review: Bisphosphonates and osteonecrosis of the jaw. Ann Intern Med. 2006; 144:753-761.
89. Ruggiero SL, Gralow J, Marx RE, et al. Practical guidelines for the prevention, diagnosis and treatment of osteonecrosis of the jaw in patients with cancer. J Oncol Pract. 2006;2:7-14.
90. Grbic JT, Landesberg R, Lin SQ, et al. Incidence of osteonecrosis of the jaw in women with postmenopausal osteoporosis in the health outcomes and reduced incidence with zoledronic acid once yearly pivotal fracture trial. J Am Dent Assoc. 2008;139:32-40.
91. Marx RE, Cillo JE Jr, Ulloa JJ. Oral bisphosphonate-induced osteonecrosis: Risk factors, prediction of risk using serum CTx testing, prevention and treatment. J Oral Maxillofac Surg. 2007;65: 2397-2410.
92. Lehrer S, Montazem A, Ramanathan L, et al. Normal serum bone markers in bisphosphonate-induced osteonecrosis of the jaws. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2008;106:389-391.
93. Mavrokokki T, Cheng A, Stein B, et al. Nature and frequency of bisphosphonate-associated osteonecrosis of the jaws in Australia. J Oral Maxillofac Surg. 2007;65:415-423.
94. Palaska PK, Cartsos V, Zavras A. Bisphosphonates and time to osteonecrosis development. Oncologist. 2009;14:1154-1166.
95. American Dental Association Council on Scientific Affairs. Dental management of patients receiving oral bisphosphonate therapy. Expert Panel recommendations. J Am Dent Assoc. 2006;137:1144-1150.
96. ASBMR Task Force on Bisphosphonate-Associated ONJ. Bisphosphonate- associated osteonecrosis of the jaw: Report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res. 2007;22:1479-1491.
97. Banal F, Briot K, Ayoub G, et al. Unilateral anterior uveitis complicating zoledronic acid therapy in prostate cancer [letter to the editor]. J Rheumatol. 2008;35:2458-2459.
98. Benderson D, Karakunnel D, Kathuria S, Badros A. Scleritis complicating zoledronic acid infusion. Clin Lymphoma Myeloma Leuk. 2006;7:145-147.
99. El Saghir NS, Otrock ZK, Bleik JH. Unilateral anterior uveitis complicating zoledronic acid therapy in breast cancer. BMC Cancer. 2005;5:156.
100. Kilickap S, Ozdamar Y, Altundag MK, et al. A case report: Zoledronic acid induced uveitis. Med Oncol. 2008;25:238-240.
101. Leung S, Ashar BH, Miller RG. Bisphosphonate associated scleritis: A case report and review. South Med J. 2005;98:733-735.
102. Procianoy F, Procianoy E. Orbital inflammatory disease secondary to a single-dose administration of zoledronic acid for treatment of postmenopausal osteoporosis. Osteoporos Int. 2010;21:1057-1058.
103. Berruti A, Tucci M, Generali D, et al. Management of the side-effects of intravenous bisphosphonates: Targeting the serum parathyroid hormone elevation. Ann Oncol. 2006;17:1854-1855.