Bisphosphonate related proximal femoral fractures
Bisphosphonate-related proximal femoral fractures are an example of insufficiency fractures, although the direct causative link remains somewhat controversial 2.
The atypical fracture pattern occurs in the proximal third of the femur, typically subtrochanteric, and may be unilateral or bilateral. Atypical femoral fractures can also occur more inferiorly to the level of the supracondylar region 1, 2, 3, 4, 6.
An atypical femoral fracture is a diagnosis of exclusion 6:
- not be spiral or comminuted
- not be femoral neck or intertrochanteric
- no evidence of malignant bone tumour (primary or metastatic)
- not be periprosthetic
The rate of this fracture as pattern outlined above in women who are treated continuously with bisphosphonates is 1 in 1000 compared to 0.2 in 1000 for untreated women 1. They occur in older, postmenopausal women 1.
Overall, the risk for all types (i.e. both typical and atypical) of femoral fractures is lower in women who take bisphosphonates 5, 6.
Most patients have been on long-term bisphosphonate therapy (> 3-5 years) and report a weeks-to-months history of thigh or groin pain 1, 2, 5, 6. Fractures can be atraumatic or result from a low-energy mechanism (e.g. fall from standing height) 1, 4, 5. They are often bilateral; if the patient has contralateral pain, the opposite femur should also be imaged.
A direct link between bisphosphonate use and atypical femoral fractures has not been unquestionably proven due to a lack of high-quality data 2, 5.
The theory that has been proposed is prolonged bisphosphonate use suppresses bone remodelling, leading to microdamage that would normally be repaired but is inhibited, thus increasing skeletal fragility 2, 3, 4.
- changes first occur within the lateral cortex of the proximal femur with cortical thickening and other changes of insufficiency fractures 1,2,6
- incomplete fractures affect the lateral cortex only 6
- complete fractures are typically transverse, sometimes oblique (<30 degrees), and can have a 'beaked' appearance of one cortex 3,4,6
- increased osteoblastic activity (i.e. uptake) in the lateral proximal femur on Tc-99m bone scan 1
Early changes will follow the pattern of insufficiency fractures with the lateral periosteum and cortex being initially affected 6.
Fractures have the following pattern 6:
- T1: low signal fracture line; diffuse low marrow signal
- T2 and STIR: low signal fracture line; diffuse high marrow signal
Treatment and prognosis
There is no consensus on treatment (conservative vs operative) and the length for which bisphosphonates should be prescribed 2,3.
Delayed fracture healing occurs in ~25% of cases 4. Healing of atypical fractures and restoration of bone quality can be aided by teriparatide, a recombinant human parathyroid hormone (rhPTH) 7,8.
Proximal femoral fractures
proximal femoral fracture
- femoral head fracture (Pipkin classification)
- femoral neck fracture (Garden classification)
- trochanteric fracture
- bisphosphonate-related proximal femoral fractures
- 1. Porrino JA, Kohl CA, Taljanovic M et-al. Diagnosis of proximal femoral insufficiency fractures in patients receiving bisphosphonate therapy. AJR Am J Roentgenol. 2010;194 (4): 1061-4. doi:10.2214/AJR.09.3383 - Pubmed citation
- 2. Yoon RS, Hwang JS, Beebe KS. Long-term bisphosphonate usage and subtrochanteric insufficiency fractures: a cause for concern?. J Bone Joint Surg Br. 2011;93 (10): 1289-95. doi:10.1302/0301-620X.93B10.26924 - Pubmed citation
- 3. Isaacs JD, Shidiak L, Harris IA et-al. Femoral insufficiency fractures associated with prolonged bisphosphonate therapy. Clin. Orthop. Relat. Res. 2010;468 (12): 3384-92. doi:10.1007/s11999-010-1535-x - Free text at pubmed - Pubmed citation
- 4. Edwards BJ, Bunta AD, Lane J et-al. 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. 2013;95 (4): 297-307. doi:10.2106/JBJS.K.01181 - Free text at pubmed - Pubmed citation
- 5. Rizzoli R, Akesson K, Bouxsein M et-al. Subtrochanteric fractures after long-term treatment with bisphosphonates: a European Society on Clinical and Economic Aspects of Osteoporosis and Osteoarthritis, and International Osteoporosis Foundation Working Group Report. Osteoporos Int. 2011;22 (2): 373-90. doi:10.1007/s00198-010-1453-5 - Free text at pubmed - Pubmed citation
- 6. Haworth AE, Webb J. Skeletal complications of bisphosphonate use: what the radiologist should know. Br J Radiol. 2012;85 (1018): 1333-42. doi:10.1259/bjr/99102700 - Free text at pubmed - Pubmed citation
- 7.Chiang CY, Zebaze RM, Ghasem-Zadeh A et-al. Teriparatide improves bone quality and healing of atypical femoral fractures associated with bisphosphonate therapy. Bone. 2013;52 (1): 360-5. doi:10.1016/j.bone.2012.10.006 - Pubmed citation
- 8. Gagnon C, Li V, Ebeling PR. Osteoporosis in men: its pathophysiology and the role of teriparatide in its treatment. Clin Interv Aging. 2009;3 (4): 635-45. Free text at pubmed - Pubmed citation