Case study: bisphosphonates and a tale of two femurs

Bisphosphonates including alendronic acid are widely prescribed for bone protection. They have a safe side effect profile and are well tolerated. A rare but serious side effect of bisphosphonates is atypical femoral fracture (AFF). There are few cases reported in literature. Our case report talks about an older female who presented under our care with bilateral femoral shaft fractures sustained after a fall. The fractures were atypical in nature and upon enquiry, it transpired that she was on long term alendronic acid.

The patients should be counselled regarding the side effects and have frequent monitoring when on bisphosphonates. Moreover, clinicians should also be aware of the same when prescribing them.

Case report

A 92-year-old female presented to A&E after sustaining a fall. She had tripped on a curb. She was unable to bear weight and was complaining of pain in both thighs. She denied any prodromal symptoms prior to fall or head injury during the fall. She had a background of ischemic heart disease, osteoarthritis, rheumatoid arthritis, and hypertension, all of which were managed medically. She was mildly frail and lived alone. She was independent with her activities of daily life.

Her medications included alendronic acid along with calcium supplements, co-codamol, aspirin, bisoprolol, furosemide and lercandipine. On examination, both thighs were swollen and tender. Her lower limbs were neurovascularly intact. X-rays of both femurs (Figures 1 and 2) showed transverse fracture on the left proximal femoral shaft and spiral fracture on the right proximal femoral shaft. Both of which are atypical femoral shaft fractures.

The orthogeriatric team felt that the AFFs could be due to long term alendronic acid use. She was optimised before she underwent bilateral femoral long intramedullary nail procedure.

Upon detailed history taking, it was found that she had previously been on alendronic acid for 10 years, had a one-year drug holiday and was taking it for the past three years prior to the presentation. The Fracture Liaison team advised no further bone protection. Alendronic acid was stopped. She had an uneventful postoperative course. She was discharged to an intermediate care facility for further rehabilitation.

According to the patient she was not made aware of this side effect, which is associated with long term alendronic acid use. She gave consent for her case to be shared to increase awareness about this side effect and better follow-ups and monitoring.

Discussion: prolonged use of bisphosphonates

Older people are at risk of osteoporosis and one in two women and one in five men aged over 50 years will suffer an osteoporotic fracture in their lifetime.¹ One of the components of bone protection treatment is the use of bisphosphonates. Bisphosphonates are a class of drugs which prevent loss of bone density by inhibiting the digestion of bone, encouraging osteoclasts to undergo apoptosis and cell death, thereby slowing bone loss. Despite the benefits, it does have side effects ranging from alopecia, anaemia to rarer ones such as atypical femoral fracture as reported.²

The prolonged use of bisphosphonates is thought to cause atypical femoral fracture(AFF) by suppression of bone turnover leading to accumulation of micro damage and alteration of collagen crosslinking, thus impeding bone remodelling.^3-5 The prolonged use of bisphosphonates therapy increases the risk and incidence of atypical AFFs.⁶ The AFFs are more common in patients who have been exposed to long-term bisphosphonates, usually for more than 3 years.³

The current guidelines recommend the need for antiresorptive drug therapies for osteoporosis to be reassessed after 3–5 years of continuous use and clinical benefits of a “drug holiday”.⁷

The management for AFFs consists of medical and orthopaedic care and depends on the grade and severity of the fracture. Our patient had complete bilateral fractures, our approach included discontinuing the bisphosphonate, assessing for calcium and vitamin D deficiency along with appropriate supplementation and Intramedullary nailing.

 Learning points

1. Clinicians need to be aware that the long-term bisphosphonate use can result in atypical femoral fracture. They should adhere to the guidelines for optimum duration, imaging, drug holiday when prescribing bisphosphonates.
2. The presence of atypical femoral fractures should alert clinicians to take a detailed drug history including the long-term bisphosphonate use.
3. Patients need to be provided full information regarding the risk and benefits of the long-term bone protection therapy.

Muzaffar Arshad Mirza, Adewale Olaniyan, Raphael Golez, Muhammad Rahmani

 References

1. Van Staa, T.P., Dennison, E.M., Leufkens, H.G.M. and Cooper, C., 2001. Epidemiology of fractures in England and Wales. Bone, [online] 29(6), pp.517–522. https://doi.org/10.1016/S8756-3282(01)00614-7
2. Joint Formulary Committee (JFC), 2024. Alendronic Acid. London: BMJ Group and Pharmaceutical Press. Available at: [https://bnf.nice.org.uk/drug/Alendronicacid.html] [Accessed 4th April 2024]
3. Shane, E., Burr, D., Abrahamsen, B, et al. Atypical Subtrochanteric and Diaphyseal Femoral Fractures: Second Report of a Task Force of the American Society for Bone and Mineral Research. Journal of Bone and Mineral Research 2014 [online] 29(1), pp.1–23. https://doi.org/10.1002/jbmr.1998.
4. Lockwood, M., Banderudrappagari, R., Suva, L.J. and Makhoul, I., 2019. Atypical femoral fractures from bisphosphonate in cancer patients – Review. Journal of Bone Oncology, [online] 18, p.100259. https://doi.org/10.1016/j.jbo.2019.100259.
5. Onafowokan, O.O., 2021. Atypical bilateral femoral fractures: a rare adverse effect of long-term bisphosphonate use. BMJ Case Reports, [online] 14(9), p.e246156. https://doi.org/10.1136/bcr-2021-246156.
6. Black, DM, Geiger EJ, Eastell R, Vittinghoff E, et al, 2020. Atypical Femur Fracture Risk versus Fragility Fracture Prevention with Bisphosphonates. New England Journal of Medicine, [online] 383(8), pp.743–753. https://doi.org/10.1056/NEJMoa1916525.
7. Tile L, Cheung AM., 2020. Atypical femur fractures: current understanding and approach to management. Therapeutic Advances in Musculoskeletal Disease, [online] 12, p.1759720X2091698. https://doi.org/10.1177/1759720X20916983.