A 36-year-old female, with a history of osteoporosis and long-term exposure to alendronate, presented to the emergency department with complaints of sudden onset pain and disability in the right hip, without a significant trauma.
A 36-year-old female presented to the emergency department with complaints of sudden onset pain and disability in the right hip, without a significant trauma. The patient had a history of osteoporosis secondary to renal insufficiency and long-standing exposure to prednisone in the setting of kidney transplantation. She had been treated with alendronate in the previous seven years.
Radiographs of the right hip showed a simple, transverse fracture (type A of the AO comprehensive classification of subtrochanteric fracture) with medial cortical spike in the proximal third of the right femur diaphysis (Figure 1). Additionally, a discrete thickening of the lateral aspect of the subtrochanteric cortex at the fracture level is also appreciated.
The subtrochanteric region of the femur is one of its strongest parts, stress fractures being uncommon. Subtrochanteric fatigue fractures have been described in athletes. In the elderly, subtrochanteric insufficiency fractures have been reported as isolated cases in hypophosphatemic osteomalacia, pycnodysostosis, or on fluoride therapy.
Alendronate is a potent inhibitor of bone resorption by inducing osteoclast apoptosis. It is a first-line therapy for osteoporotic fractures prevention, reducing their incidence by 50%. When discontinued after 5 years, its effect remains for 5 years thereafter, without increased fracture risk.
In the past years, concerns have been raised over the potential harmful effects of prolonged bone turnover suppression. Observational studies reported an increasing number of subtrochanteric fractures associated with long-lasting alendronate. Complementary histomorphometric analysis supported the hypothesis that long-term alendronate may severely suppress bone turnover, limiting microdamage repair. As microcracks co-localize within highly mineralized regions, the subtrochanteric cortical bone becomes susceptible to microdamage, stress reactions and fractures, and eventually complete fractures. Co-administration of steroids, as in the case shown, has also been referred as a predisposing factor.
These fractures exhibit a not previously reported radiological pattern that likely represents a new form of insufficiency fracture. It is characterized by a simple, transverse fracture (type A of the AO comprehensive classification of subtrochanteric fracture), with medial cortical spike, and cortical thickening in the lateral subtrochanteric region, nicely exemplified by the case exposed. In addition, the majority of patients experiences prodromal pain on the affected limb. Poor rate of union despite discontinuing alendronate and bilateralism present in half of patients point to the systemic nature of this disorder.
Although primarily studied with plain films, other imaging techniques as bone scintigraphy and magnetic resonance can also mirror the sequence of pathologic events that lead to the complete insufficiency fracture and may even be more sensitive for its detection.
However, a definite causal link with alendronate therapy has been disputed by a large Danish study which suggested that these atypical fractures may simply reflect the higher risk for fracture of patients on alendronate. It included low- and high-energy fractures, a limited number of patients on long-term alendronate with subtrochanteric fracture, and all types of morphological patterns of subtrochanteric fractures making direct comparison with the previous studies not straightforward.
The challenge to the clinical community is how to avoid exposing patients to undue risks of long-term side effects while reducing the risk of fractures in high-risk patients. Not only the time and dose but also the absolute incidence must be considered, so any potential risk can be weighed against the benefit of avoiding osteoporotic fractures. The evidence at the moment is split between observations indicating that low-energy subtrochanteric femur fractures associated with long-term alendronate use have peculiar and consistent radiological and clinical features, clinical trials indicating long-term safety of alendronate, and epidemiological and pharmacoepidemiological observations indicating that this fracture may share the epidemiology and treatment response characteristic of osteoporotic fractures. Further research, perhaps using advanced skeletal imaging in long-term bisphosphonate users, will hopefully elucidate biological plausibility.
Subtrochanteric insufficiency fractures associated with long-term exposure to alendronate
Given the long-term alendronate use, presence of osteoporosis, and typical transverse fracture appearance on imaging, a bisphosphonate-related subtrochanteric incomplete fracture is the primary consideration.
Based on the patient’s history (long-term use of alendronate and concurrent glucocorticoid therapy), characteristic radiological findings (transverse-type fracture, lateral cortical thickening, medial spur-like appearance), and clinical symptoms (sudden onset hip pain, functional impairment), the most likely diagnosis is:
Subtrochanteric Incomplete Femoral Fracture (“Atypical Femoral Fracture”) Due to Long-Term Bisphosphonate Use
1. Treatment Strategy
• Surgical Intervention: For fractures with significant displacement or instability, intramedullary nailing or locking plate fixation is usually recommended to stabilize the fracture.
• Medication Adjustment: Assess the need to suspend or discontinue bisphosphonate therapy; after fracture healing, re-evaluate osteoporosis management and consider switching to other anti-osteoporotic medications (such as teriparatide) or an intermittent dosing strategy.
• Nutritional Support: Supplement calcium and vitamin D; other nutrients may be added as indicated by bone metabolism markers and electrolyte levels.
• Pain Management: During the postoperative or conservative treatment period, use oral or intravenous analgesics, adjusting as needed based on the patient’s pain level and tolerance.
2. Rehabilitation/Exercise Prescription (FITT-VP Principle)
• Early Phase (1-2 weeks post-fracture stabilization or surgery):
(a) Frequency: Perform 1-2 sessions of mild activity daily, such as isometric quadriceps exercises at the bedside to prevent muscle atrophy.
(b) Intensity: Keep intensity low and avoid bearing weight on the hip.
(c) Time: 5-10 minutes per session, adjusted according to pain tolerance.
(d) Type: Mainly lower-extremity isometric exercises and ankle pumps that do not compromise fracture stability.
(e) Progression: Gradually increase session frequency or duration based on pain and healing status.
• Intermediate Phase (4-6 weeks post-surgery or partial fracture healing):
(a) Frequency: Increase to 3-4 sessions per week of walking exercises with assistive devices.
(b) Intensity: Partial weight-bearing with supportive equipment, monitoring hip pain and muscle strength.
(c) Time: 10-15 minutes per session, progressively increasing to 20-30 minutes.
(d) Type: Under professional guidance, work on range-of-motion exercises for the lower limbs and core muscle stabilization.
(e) Progression: Once hip pain subsides and there is good evidence of fracture healing, gradually reduce reliance on assistive devices and transition to partial independent walking.
• Late Phase (12 weeks post-surgery or after fracture healing):
(a) Frequency: 3-5 regular sessions of exercise per week, gradually returning to typical daily activity levels.
(b) Intensity: Increase weight-bearing and resistance training according to fracture healing status and bone density results, but avoid high-impact activities (running, jumping, etc.).
(c) Time: 20-30 minutes per session, progressively extending to 45 minutes or more.
(d) Type: May include aquatic therapy (swimming, water walking), on-land walking, mild resistance exercises, or balance training.
(e) Progression: As healing and strength improve, gradually increase both load and resistance while avoiding excessive fatigue or re-injury.
Important Considerations
• Regularly monitor fracture healing and bone metabolism markers. If hip pain worsens or mobility becomes more limited, seek medical attention promptly.
• For patients with osteoporosis, emphasize fall prevention and environmental safety during exercise; use protective equipment or assistive devices if needed.
• Coordinate long-term medication use and bone health management with specialists to maintain a balance between fracture healing and preventing additional fractures.
Disclaimer: The above analysis report is for reference only and does not replace an in-person consultation or professional medical advice. If you have any questions or experience any discomfort, please consult a professional medical institution or specialist promptly.
Subtrochanteric insufficiency fractures associated with long-term exposure to alendronate
