Arch Hand Microsurg.  2024 Dec;29(4):211-219. 10.12790/ahm.24.0033.

Sclerotic lines around the radial tuberosity of the proximal radius in patients with atypical femoral fractures associated with long-term bisphosphonate use: a preliminary report

• Kim YH
• Cha SM
• Ga IH

• KMID: 2561369
• DOI: http://doi.org/10.12790/ahm.24.0033

Abstract

Purpose
Sclerotic lines have been detected at specific locations on the forearm and metaphysis of the lower extremities (femur and tibia) in some patients with atypical femoral fractures (AFFs) associated with long-term bisphosphonate (BP) use. Herein, we present our preliminary data relating to the factors associated with the occurrence of sclerotic lines in patients diagnosed with AFFs.
Methods
We inspected the clinical charts of patients who were prescribed BPs at our institution between 2010 and 2020. Fifty-six patients were finally investigated, including patients with sclerotic line lesions at the radial tuberosity (21 patients), and those without any pathognomonic lesions on either radius on a simple radiograph (35 patients).
Results
No significant between-group differences in basic demographic characteristics, bone mineral density, or the total period of BP administration were observed (p>0.05). Multivariate analyses of the variables that exhibited significant between-group differences in the univariate analyses demonstrated that the time since the last BP administration at the time of AFF diagnosis (odds ratio [OR], 0.441) and the concurrent presence of similar lines on the femur (OR, 36.00) were significantly associated with the presence of sclerotic lines on the proximal radius. The cutoff time after the last BP administration at the time of AFF diagnosis was 16.5 months, which may serve as a predictor for the development of a sclerotic line around the radial tuberosity.
Conclusion
Sclerotic lines on the proximal radius were detected more frequently in patients who had been recently treated with a BP or had similar lines on the lower extremities.

Keyword

Atypical fracture; Femur; Ulna; Radius; Sclerotic lines

Figure

• 

  Fig. 1. (A) Multiple sclerotic lines were detected around the radial tuberosity and proximal ulnas (arrows) in a 62-year-old woman. An incomplete atypical fracture (endosteal and periosteal thickening) was found at the ulnar diaphysis (circle). The bisphosphonate (BP) had been stopped 8 months previously, with a history of atypical femoral fractures (AFFs) in both femurs. The total time of BP administration was 85 months. (B) A 72-year-old woman had sclerotic lines around the radial tuberosity and proximal ulnas (arrows). An incomplete atypical fracture (endosteal and periosteal thickening) was detected at the radial diaphysis (circle). The BP had been stopped 14 months ago, with a history of an AFF on one femur. The total time of BP administration was 73 months. Lesions of an incomplete radial fracture were detected 8 months after the AFF diagnosis.

• 

  Fig. 2. A receiver operating characteristic curve revealing the optimal cutoff value predicting the maximal time from final bisphosphonate treatment.

• 

  Fig. 3. (A) A typical “zebra line” in a pediatric patient. (B) Typical sclerotic lines associated with bisphosphonate (BP) use (arrows). These lines were not parallel. Additionally, unlike zebra lines in the pediatric population, the lengths of the lines were not proportional to the diameter of the metaphysis where the lines were located. Arthroplasty was performed 6 years after BP treatment.

• 

  Fig. 4. (A) A 70-year-old woman presented with a complete radioulnar fracture after a fall. A rare lesion at the distal ulna (circle) prompted a further evaluation of any association with long-term bisphosphonate (BP) use. The BP had been stopped 12 months ago, and an incomplete atypical femoral fracture (AFF) was detected 74 months after BP treatment. (B) At the time of the forearm fracture, an incomplete AFF was cautiously diagnosed (circle), but sclerotic lines were detected on the distal femur (arrows). The arthroplasties were performed 2 years after BP administration.

• 

  Fig. 5. An 82-year-old woman presented with a left-side complete atypical femoral fracture (AFF) after a fall. Definitive lines were found on the distal femur (yellow circle). During reaming for interlocking nails, the lines disappeared (red circle). The right femur was fixed 7 months previously due to an AFF.

Reference

References

1. Boivin GY, Chavassieux PM, Santora AC, Yates J, Meunier PJ. Alendronate increases bone strength by increasing the mean degree of mineralization of bone tissue in osteoporotic women. Bone. 2000; 27:687–94.

2. Bone HG, Hosking D, Devogelaer JP, et al. Ten years’ experience with alendronate for osteoporosis in postmenopausal women. N Engl J Med. 2004; 350:1189–99.

3. Eastell R, Barton I, Hannon RA, Chines A, Garnero P, Delmas PD. Relationship of early changes in bone resorption to the reduction in fracture risk with risedronate. J Bone Miner Res. 2003; 18:1051–6.

4. Allen MR, Iwata K, Phipps R, Burr DB. Alterations in canine vertebral bone turnover, microdamage accumulation, and biomechanical properties following 1-year treatment with clinical treatment doses of risedronate or alendronate. Bone. 2006; 39:872–9.

5. Tan SH, Saseendar S, Tan BH, Pawaskar A, Kumar VP. Ulnar fractures with bisphosphonate therapy: a systematic review of published case reports. Osteoporos Int. 2015; 26:421–9.

6. Chiang GS, Koh KW, Chong TW, Tan BY. Stress fracture of the ulna associated with bisphosphonate therapy and use of walking aid. Osteoporos Int. 2014; 25:2151–4.

7. Moon J, Bither N, Lee T. Atypical forearm fractures associated with long-term use of bisphosphonate. Arch Orthop Trauma Surg. 2013; 133:889–92.

8. Ang BF, Koh JS, Ng AC, Howe TS. Bilateral ulna fractures associated with bisphosphonate therapy. Osteoporos Int. 2013; 24:1523–5.

9. Tang ZH, Kumar VP. Alendronate-associated ulnar and tibial fractures: a case report. J Orthop Surg (Hong Kong). 2011; 19:370–2.

10. Bjørgul K, Reigstad A. Atypical fracture of the ulna associated with alendronate use. Acta Orthop. 2011; 82:761–3.

11. Stathopoulos KD, Kosmidis C, Lyritis GP. 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. 2011; 11:208–11.

12. Shimada Y, Ishikawa T, Endo J, et al. Treatment of atypical ulnar fractures associated with long-term bisphosphonate therapy for osteoporosis: autogenous bone graft with internal fixation. Case Rep Orthop. 2017; 2017:8602573.

13. Oh BH, Heo YM, Yi JW, Kim TG, Lee JS. Atypical fracture of the proximal shaft of the ulna associated with prolonged bisphosphonate therapy. Clin Orthop Surg. 2018; 10:389–92.

14. Cha SM, Shin HD, Ahn BK. Revision osteosynthesis after primary treatment of atypical ulnar fractures associated with bisphosphonate usage: nonunion after ordinary open reduction and internal fixation. Arch Orthop Trauma Surg. 2021; 141:1855–62.

15. Asano Y, Tajiri K, Yagishita S, Nakanishi H, Ishii T. Bilateral atypical ulnar fractures occurring after long-term treatment with bisphosphonate for 7 years and with teriparatide for 2 years: a case report. Osteoporos Int. 2020; 31:2473–6.

16. Cha SM, Shin HD. Risk factors for atypical forearm fractures associated with bisphosphonate usage. Injury. 2021; 52:1423–8.

17. Abe K, Kimura H, Yamamoto N, et al. Treatment strategy for atypical ulnar fracture due to severely suppressed bone turnover caused by long-term bisphosphonate therapy: a case report and literature review. BMC Musculoskelet Disord. 2020; 21:802.

18. Mohan PC, Howe TS, Koh JS, Png MA. Radiographic features of multifocal endosteal thickening of the femur in patients on long-term bisphosphonate therapy. Eur Radiol. 2013; 23:222–7.

19. Png MA, Koh JS, Goh SK, Fook-Chong S, Howe TS. Bisphosphonate-related femoral periosteal stress reactions: scoring system based on radiographic and MRI findings. AJR Am J Roentgenol. 2012; 198:869–77.

20. Al Muderis M, Azzopardi T, Cundy P. Zebra lines of pamidronate therapy in children. J Bone Joint Surg Am. 2007; 89:1511–6.

21. Kim SD, Cho BS. Pamidronate therapy for preventing steroid-induced osteoporosis in children with nephropathy. Nephron Clin Pract. 2006; 102:c81–7.

22. Devogelaer JP, Malghem J, Maldague B, Nagant de Deuxchaisnes C. Radiological manifestations of bisphosphonate treatment with APD in a child suffering from osteogenesis imperfecta. Skeletal Radiol. 1987; 16:360–3.

23. Samuel R, Katz K, Papapoulos SE, Yosipovitch Z, Zaizov R, Liberman UA. Aminohydroxy propylidene bisphosphonate (APD) treatment improves the clinical skeletal manifestations of Gaucher’s disease. Pediatrics. 1994; 94:385–9.

24. Siris ES, Harris ST, Rosen CJ, et al. Adherence to bisphosphonate therapy and fracture rates in osteoporotic women: relationship to vertebral and nonvertebral fractures from 2 US claims databases. Mayo Clin Proc. 2006; 81:1013–22.

25. Ogden JA. Growth slowdown and arrest lines. J Pediatr Orthop. 1984; 4:409–15.

26. Rauch F, Travers R, Munns C, Glorieux FH. Sclerotic metaphyseal lines in a child treated with pamidronate: histomorphometric analysis. J Bone Miner Res. 2004; 19:1191–3.

27. 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.

28. Dimeglio LA, Ford L, McClintock C, Peacock M. A comparison of oral and intravenous bisphosphonate therapy for children with osteogenesis imperfecta. J Pediatr Endocrinol Metab. 2005; 18:43–53.

29. Zacharin M, Bateman J. Pamidronate treatment of osteogenesis imperfecta: lack of correlation between clinical severity, age at onset of treatment, predicted collagen mutation and treatment response. J Pediatr Endocrinol Metab. 2002; 15:163–74.

30. Silverman SL, Hurvitz EA, Nelson VS, Chiodo A. Rachitic syndrome after disodium etidronate therapy in an adolescent. Arch Phys Med Rehabil. 1994; 75:118–20.