Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Osteoporosis International
Published in: Osteoporosis International 2/2015

01-02-2015 | Review

Ulnar fractures with bisphosphonate therapy: a systematic review of published case reports

Authors: S. H. S. Tan, S. Saseendar, B. H. M. Tan, A. Pawaskar, V. P. Kumar

Published in: Osteoporosis International | Issue 2/2015

Login to get access

Abstract

Summary

A systematic review of eight ulnar fractures in seven patients with bisphosphonate therapy was performed to describe the characteristics and predisposing factors. The proximal ulna is likely to be fractured, especially in the dominant limb of elderly female patients using walking aids after 7 to 15 years of bisphosphonate use.

Introduction

Long-term bisphosphonate use has been suggested to result in decreased bone remodelling and increased risk of atypical fractures. While the relationship between bisphosphonate use and atypical femoral fractures has been extensively studied, there is relative rarity and unawareness of these fractures in the forearm. We conducted a systematic review of existing case reports to better describe the characteristics and predisposing factors for fractures occurring in patients with bisphosphonate therapy.

Methods

The systematic review was conducted according to PRISMA guidelines. All studies with ulnar fractures in individuals with history of bisphosphonate use were included, with data extracted and analysed in totality.

Results

Seven patients with eight fractures are included. Predisposing factors include elderly females requiring walking aids. There is a propensity for the proximal ulna to be fractured, especially in the dominant limb used for ambulation or transfer. All patients were on bisphosphonate for 7 to 15 years. All fractures were atraumatic, non-comminuted, transverse in configuration, had localised periosteal or endosteal thickening at the fracture site and generalised cortical thickening of the diaphysis.

Conclusion

Ulnar fractures in patients with bisphosphonate therapy demonstrate features similar to those described for atypical femoral fractures, suggesting that these fractures could also possibly be due to bisphosphonate use. However, the ulna appears to be able to tolerate longer periods of alendronate use prior to fracture development. The mechanism and characteristics of these fractures additionally suggest the presence of repetitive stress that accumulates over time due to suppressed bone remodelling in patients on bisphosphonates, eventually resulting in these fractures.
Literature
1.
Black DM, Bauer DC, Schwartz AV, Cummings SR, Rosen CJ (2012) Continuing bisphosphonate treatment for osteoporosis—for whom and for how long? N Engl J Med 366:2051–2053PubMedCentralPubMedCrossRef
2.
Whitaker M, Guo J, Kehoe T, Benson G (2012) Bisphosphonates for osteoporosis—where do we go from here? N Engl J Med 366:2048–2051PubMedCrossRef
3.
Giusti A, Hamdy NA, Papapoulos SE (2010) Atypical fractures of the femur and bisphosphonate therapy: a systematic review of case/case series studies. Bone 47(2):169–180PubMedCrossRef
4.
Seraphim A, Al-Hadithy N, Mordecai SC, Al-Nammari S (2012) Do bisphosphonates cause femoral insufficiency fractures? J Orthop Traumatol 13(4):171–177PubMedCentralPubMedCrossRef
5.
Gasser AB, Morgan DB, Fleisch HA, Richelle LJ (1972) The influence of two diphosphonates on calcium metabolism in the rat. Clin Sci 43(1):31–45PubMed
6.
Tang ZH, Kumar VP (2011) Alendronate-associated ulnar and tibial fractures: a case report. J Orthop Surg (Hong Kong) 19(3):370–372
7.
Edwards BJ, Bunta AD, Lane J, Odvina C, Rao DS, Raisch DW, McKoy JM, Omar I, Belknap SM, Garg V, Hahr AJ, Samaras AT, Fisher MJ, West DP, Langman CB, Stern PH (2013) Bisphosphonates and nonhealing femoral fractures: analysis of the FDA Adverse Event Reporting System (FAERS) and international safety efforts: a systematic review from the Research on Adverse Drug Events And Reports (RADAR) project. J Bone Joint Surg Am 95(4):297–307PubMedCentralPubMedCrossRef
8.
Jamal SA, Dion N, Ste-Marie LG (2011) Atypical femoral fractures and bone turnover. N Engl J Med 365(13):1261–1262PubMedCrossRef
9.
Mashiba T, Hirano T, Turner CH, Forwood MR, Johnston CC, Burr DB (2000) Suppressed bone turnover by bisphosphonates increases microdamage accumulation and reduces some biomechanical properties in dog rib. J Bone Miner Res 15(4):613–620PubMedCrossRef
10.
Moon J, Bither N, Lee T (2013) Atypical forearm fractures associated with long-term use of bisphosphonate. Arch Orthop Trauma Surg 133(7):889–892PubMedCrossRef
11.
Shane E, Burr D, Abrahamsen B, Adler RA, Brown TD, Cheung AM, Cosman F, Curtis JR, Dell R, Dempster DW, Ebeling PR, Einhorn TA, Genant HK, Geusens P, Klaushofer K, Lane JM, McKiernan F, McKinney R, Ng A, Nieves J, O’Keefe R, Papapoulos S, Howe TS, van der Meulen MC, Weinstein RS, Whyte MP (2014) Atypical subtrochanteric and diaphyseal femoral fractures: second report of a task force of the american society for bone and mineral research. J Bone Miner Res 29(1):1–23PubMedCrossRef
12.
Breglia MD, Carter JD (2010) Atypical insufficiency fracture of the tibia associated with long-term bisphosphonate therapy. J Clin Rheumatol 16:76–78PubMedCrossRef
13.
Imai K, Yamamoto S, Anamizu Y, Horiuchi T (2007) Pelvic insufficiency fracture associated with severe suppression of bone turnover by alendronate therapy. J Bone Miner Metab 25:333–336PubMedCrossRef
14.
15.
Stathopoulos KD, Kosmidis C, Lyritis GP (2011) Atypical fractures of the femur and ulna and complications of fracture healing in a 76-year-old woman with Sjögren’s syndrome. J Musculoskelet Neuronal Interact 11(2):208–211, quiz 211PubMed
16.
Ang BF, Koh JS, Ng AC, Howe TS (2013) Bilateral ulna fractures associated with bisphosphonate therapy. Osteoporos Int 24(4):1523–1525PubMedCrossRef
17.
Osada R, Zukawa M, Kimura T (2014) Atypical ulnar fracture associated with long-term bisphosphonate use. J Orthop Sci. doi:10.1007/s00776-014-0589-0
18.
19.
Mashiba T, Mori S, Burr DB, Komatsubara S, Cao Y, Manabe T, Norimatsu H (2005) The effects of suppressed bone remodeling by bisphosphonates on microdamage accumulation and degree of mineralization in the cortical bone of dog rib. J Bone Miner Metab 23(Suppl):36–42PubMedCrossRef
20.
Somford MP, Draijer FW, Thomassen BJ, Chavassieux PM, Boivin G, Papapoulos SE (2009) Bilateral fractures of the femur diaphysis in a patient with rheumatoid arthritis on long-term treatment with alendronate: clues to the mechanism of increased bone fragility. J Bone Miner Res 24(10):1736–1740PubMedCrossRef
21.
Benford HL, McGowan NW, Helfrich MH, Nuttall ME, Rogers MJ (2001) Visualization of bisphosphonate-induced caspase-3 activity in apoptotic osteoclasts in vitro. Bone 28(5):465–473PubMedCrossRef
22.
Idris AI, Rojas J, Greig IR, Van’t Hof RJ, Ralston SH (2008) Aminobisphosphonates cause osteoblast apoptosis and inhibit bone nodule formation in vitro. Calcif Tissue Int 82(3):191–201PubMedCrossRef
23.
Wu P, Koharski C, Nonnenmann H, Vashishth D (2003) Loading on non-enzymatically glycated and damaged bone results in an instantaneous fracture. Trans Orthop Res Soc 28:404
24.
Gourion-Arsiquaud S, Faibish D, Myers E, Spevak L, Compston J, Hodsman A, Shane E, Recker RR, Boskey ER, Boskey AL (2009) Use of FTIR spectroscopic imaging to identify parameters associated with fragility fracture. J Bone Miner Res 24(9):1565–1571PubMedCentralPubMedCrossRef
25.
Wang X, Li X, Shen X, Agrawal CM (2003) Age-related changes of noncalcified collagen in human cortical bone. Ann Biomed Eng 31(11):1365–1371PubMedCrossRef
26.
Boivin G, Meunie PJ (2001) Changes in bone remodeling rate influence the degree of mineralization of bone which is a determinant of bone strength: therapeutic implications. Adv Exp Med Biol 496:123–127PubMedCrossRef
27.
Gourion-Arsiquaud S, Allen MR, Burr DB, Vashishth D, Tang SY, Boskey AL (2010) Bisphosphonate treatment modifies canine bone mineral and matrix properties and their heterogeneity. Bone 46(3):666–672PubMedCentralPubMedCrossRef
28.
Boskey AL, Spevak L, Weinstein RS (2009) Spectroscopic markers of bone quality in alendronate-treated postmenopausal women. Osteoporos Int 20(5):793–800PubMedCentralPubMedCrossRef
29.
Whyte MP (2009) Atypical femoral fractures, bisphosphonates, and adult hypophosphatasia. J Bone Miner Res 24(6):1132–1134PubMedCrossRef
30.
31.
Eriksen EF, Díez-Pérez A, Boonen S (2014) Update on long-term treatment with bisphosphonates for postmenopausal osteoporosis: a systematic review. Bone 58:126–135PubMedCrossRef
32.
Levis S, Theodore G (2012) Summary of AHRQ’s comparative effectiveness review of treatment to prevent fractures in men and women with low bone density or osteoporosis: update of the 2007 report. J Manag Care Pharm 18(4 Suppl B):S1–S15, discussion S13PubMed
33.
Neviaser AS, Lane JM, Lenart BA, Edobor-Osula F, Lorich DG (2008) Low-energy femoral shaft fractures associated with alendronate use. J Orthop Trauma 22(5):346–350PubMedCrossRef
34.
35.
Black DM, Schwartz AV, Ensrud KE, Cauley JA, Levis S, Quandt SA et al (2006) Effects of continuing or stopping alendronate after 5 years of treatment: the Fracture Intervention Trial Long-term Extension (FLEX)—a randomized trial. JAMA 296:2927–2938PubMedCrossRef
36.
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 350:1189–1199PubMedCrossRef
37.
Tonino RP, Meunier PJ, Emkey R, Rodriguez-Portales JA, Menkes CJ, Wasnich RD et al (2000) Skeletal benefits of alendronate: 7-year treatment of postmenopausal osteoporotic women. Phase III Osteoporosis Treatment Study Group. J Clin Endocrinol Metab 85:3109–3115PubMed
38.
Shane E, Burr D, Ebeling PR, Abrahamsen B, Adler RA, Brown TD, Cheung AM, Cosman F, Curtis JR, Dell R, Dempster D, Einhorn TA, Genant HK, Geusens P, Klaushofer K, Koval K, Lane JM, McKiernan F, McKinney R, Ng A, Nieves J, O’Keefe R, Papapoulos S, Sen HT, van der Meulen MC, Weinstein RS, Whyte M (2010) American Society for Bone and Mineral Research. Atypical subtrochanteric and diaphyseal femoral fractures: report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res 25(11):2267–2294PubMedCrossRef
39.
40.
Mackay D, Wood L, Rangan A (2000) The treatment of isolated ulnar fractures in adults: a systematic review. Injury 31(8):565–570PubMedCrossRef
41.
Saka G, Sağlam N, Kurtulmuş T, Özer C, Uğurlar M, Akpınar F (2013) Interlocking intramedullary ulna nails in isolated ulna diaphyseal fractures: a retrospective study. Acta Orthop Traumatol Turc 47(4):236–243PubMedCrossRef
42.
Saita Y, Ishijima M, Mogami A, Kubota M, Baba T, Kaketa T, Nagao M, Sakamoto Y, Sakai K, Kato R, Nagura N, Miyagawa K, Wada T, Liu L, Obayashi O, Shitoto K, Nozawa M, Kajihara H, Gen H, Kaneko K (2014) The fracture sites of atypical femoral fractures are associated with the weight-bearing lower limb alignment. Bone 66:105–110PubMedCrossRef
43.
Chen LP, Chang TK, Huang TY, Kwok TG, Lu YC (2014) The correlation between lateral bowing angle of the femur and the location of atypical femur fractures. Calcif Tissue Int 95(3):240–247. doi:10.​1007/​s00223-014-9887-y
Metadata
Title
Ulnar fractures with bisphosphonate therapy: a systematic review of published case reports
Authors
S. H. S. Tan
S. Saseendar
B. H. M. Tan
A. Pawaskar
V. P. Kumar
Publication date
01-02-2015
Publisher
Springer London
Published in
Osteoporosis International / Issue 2/2015
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-014-2885-0

Other articles of this Issue 2/2015

Osteoporosis International 2/2015 Go to the issue

Original Article

Peak muscle mass in young men and sarcopenia in the ageing male

Original Article

Nationwide cohort study of hip fractures: time trends in the incidence rates and projections up to 2035

Letter

Relationship between fetuin-A levels and bone mineral density

Original Article

Subsequent fracture rates in a nationwide population-based cohort study with a 10-year perspective

Original Article

Reproducibility of jumping mechanography and traditional measures of physical and muscle function in older adults

Original Article

Incidence of ocular side effects with intravenous zoledronate: secondary analysis of a randomized controlled trial