AFOS 2025 Guidance on Atypical Femoral Fractures Associated with Osteoporosis Treatment

<h2 id="introduction">Introduction</h2><ul><li>Atypical femoral fractures (AFFs) are an uncommon but serious complication associated with long-term anti- resorptive therapy for osteoporosis. This study aimed to develop consensus-based recommendations for the clinical management of AFFS across the Asian Federation of Osteoporosis Societies (AFOS), with the goal of harmonizing clinical practice and improving patient outcomes.</li><li>Atypical femoral fractures (AFFs) are defined as low-energy fractures of the femoral shaft, typically occurring between the distal aspect of the lesser trochanter and the proximal supracondylar flare.</li><li>The absolute risk of atypical femoral fractures (AFFs) with bisphosphonate therapy is low, with reported incidence ranging from 3.2 to 50 per 100,000 person-years.</li><li>In most patients, the benefits of anti-resorptive therapy in preventing fragility fractures outweigh the low risk of AFFs, especially when appropriate monitoring and preventive measures are in place.</li></ul><h2 id="diagnosis">Diagnosis of Osteoporosis</h2><p>Early recognition of atypical femoral fractures (AFFs) requires high clinical suspicion in patients on long-term anti- resorptive therapy who present with persistent dull pain in the thigh, hip, groin, or knee. Symptoms often appear weeks to months before fracture. Complete AFFs usually occur with minimal trauma, such as walking or standing from a seated position.</p><p><strong>Recommended imaging modalities includes:</strong></p><ul><li>X-rays: Anteroposterior and lateral full-length femoral radiographs are first-line due to due to a 28-40% incidence of contralateral involvement.</li><li>Dual-Energy X-ray Absorptiometry (DXA): Extended femoral views help detect early cortical changes.&nbsp;</li><li>Computed Tomography (CT): Used when a fracture line is suspected on X-ray or DXA. It gives detailed visualization of cortical lucency and periosteal thickening.</li><li>MRI: Useful when Radiographs and DXA does not reveal definitive fractures, Lateral cortical thickening is observed without cortical lucency, Bone marrow edema alone suggests a stress reaction, Edema with cortical lucency confirms incomplete AFFS.</li></ul><h2 id="prevention">Prevention and screening</h2><p>Patients on bisphosphonates should be reassessed after 3-5 years to consider continuation or a drug holiday. The International Society for Clinical Densitometry (ISCD) currently recommends the following screening measures for patients on antiresorptive agents.</p><ul><li>Routine bilateral full-length femoral imaging is recommended after three years of continuous therapy, especially in patients concurrently on glucocorticoids.</li><li>Bilateral femoral imaging is mandatory in patients on anti-resorptive therapy presenting with groin, thigh, or hip pain, to exclude impending or incomplete AFFs.</li></ul><h2 id="affs">Management of AFFs</h2><ul><li>Four AFOS member countries-Thailand, Malaysia, South Korea, and Hong Kong-have published national or regional guidelines for the management of AFFs.</li><li>Management of incomplete AFFs should be individualized, guided by patient symptoms and imaging findings.&nbsp;</li></ul><p><strong><u>Symptomatic patients with functional limitation:</u></strong></p><p>Patients with weight-bearing pain and X-ray findings such as periosteal reaction, lateral cortical thickening, or the "dreaded black line" should undergo prophylactic intramedullary nailing. Early surgery greatly reduces progression to complete fracture and achieves union rates up to 97%, compared with high failure rates with conservative treatment.</p><p><strong><u>Mildly symptomatic patients without functional limitation:</u></strong></p><p>A trial of conservative management may be attempted, including non-weight-bearing measures, assistive devices, and regular radiographic monitoring. Surgery should be considered if there is no improvement within 2-3 months.&nbsp;</p><p><strong><u>Asymptomatic patients with incidental radiographic findings:</u></strong></p><p>Patients with isolated cortical thickening and no pain can be managed conservatively with activity modification and periodic imaging. MRI or bone scintigraph may help to assess for bone marrow edema or metabolic activity suggestive of a stress reaction</p><p><strong><u>Japanese practice pattern:</u></strong></p><p>Treatment decisions are often based on radiographic patterns with subtrochanteric lesions more likely to need surgery than diaphyseal lesions, especially when a radiolucent line is present.</p><p><strong><u>Teriparatide (PTH 1-34):</u></strong></p><p>Shows potential benefit in selected AFF cases. It may reduce delayed union and nonunion and speed up fracture healing. Teriparatide is increasingly used in clinical practice, often as an adjunct to surgical treatment.</p><h3>1. Osteoporosis management following AFFs</h3><p>Management should be individualized to support fracture healing, prevent future fractures, and reduce drug- related risks.</p><ul><li>Discontinuation of Anti-resorptive Therapy<ul><li>Stop anti-resorptive drugs immediately after an AFF, including bisphosphonates and denosumab.&nbsp;</li><li>Denosumab discontinuation is challenging due to rebound bone loss and increased risk of vertebral fractures.</li><li>A bisphosphonate "bridge" is often used after stopping denosumab to reduce rebound risk, but this approach requires caution in AFF patients, especially those with prior bisphosphonate exposure.</li><li>A significant number of denosumab-associated AFFs occur in patients previously treated with bisphosphonates, suggesting additive risk with sequential therapy.</li></ul></li><li>Alternative Treatments<ul><li>Non-bisphosphonate options such as raloxifene and anabolic agents (teriparatide, romosozumab) may be considered.<br><strong>Evidence suggests:</strong></li><li>Romosozumab maintains hip BMD and improves spine BMD</li><li>Teriparatide after denosumab may reduce hip BMD</li><li>Specialist referral and Fracture Liaison Service involvement are escor safe post-AFF care.</li><li>All anabolic therapies cause rapid BMD loss after discontinuation, so long-term treatment planning is essential.</li><li>Treatment decisions should be based on total anti-resorptive exposure, fracture risk, and future transition strategy, ideally planned before starting denosumab.</li></ul></li></ul><h3>2. Evaluation of Secondary Osteoporosis</h3><ul><li>All patients after AFFs should be evaluated for secondary causes of bone fragility, especially those without prior metabolic work-up. Assessment is particularly important in high-risk patients.</li><li><strong>Key conditions to evaluate:</strong><ul><li>History of bariatric surgery or malabsorption disorders</li><li>Trace mineral deficiencies (e.g., copper), which may increase fall risk</li><li>Vitamin D and calcium deficiency or malabsorption</li><li>Hypercalciuria, detected by 24-hour urine calcium testing, even without kidney stones</li><li>Normocalcemic hyperparathyroidism, assessed after correcting vitamin D levels</li></ul></li></ul><p>Identifying and correcting these causes may improve bone strength and sometimes reduce the need for drug therapy.</p><h3>3. Consideration of Anabolic Therapy</h3><ul><li>Anabolic agents help both fracture healing and bone density recovery after AFFs.&nbsp;</li><li>Teriparatide is the most widely studied anabolic therapy in AFFs.</li><li>Evidence shows that teriparatide:<ul><li>Improves fracture healing</li><li>In surgically treated complete AFFs, healing rates increased from 51% to 76%</li></ul></li><li>Anabolic therapy may be especially useful in patients with delayed healing or high fracture risk. In incomplete AFFs treated with prophylactic surgery, healing rates improved significantly (43%<br>90%).</li><li>Although most evidence comes from case series and observational studies, findings consistently support the use of anabolic therapy for both fracture healing and long-term bone health after AFFs.</li><li>Cyclical teriparatide therapy (e.g., 3 months on/3 months off) may preserve bone turnover while reducing cost and side effects, but BMD gains are smaller than with continuous therapy.</li><li>Cyclical regimens are not FDA-approved and may face reimbursement and regulatory limitations. More research is needed to confirm long-term benefits.</li><li>Because BMD rapidly declines after stopping anabolic agents, maintenance therapy is essential to preserve gains and prevent new fractures.</li><li>Raloxifene may be considered after teriparatide in selected postmenopausal women at lower fracture risk or those unable to use stronger anti-resorptives.</li><li><strong>Duration limit for Teriparatide is maximum 2 years</strong></li><li>A planned transition to maintenance therapy (often an anti-resorptive) is necessary for long-term skeletal protection.</li><li>In patients with persistent high fracture risk, even after AFF healing and correction of secondary causes, sequential or cyclical anabolic therapy may be considered in carefully selected cases.</li><li>Individualized treatment planning, based on fracture risk, access, cost, and patient preference, is critical for optimal outcomes.</li></ul><h2 id="osteoporosis">Osteoporosis management after AFFS - Therapeutic dilemma</h2><ul><li>Managing osteoporosis after AFFs is clinically challenging.</li><li>Stopping anti-resorptive therapy is usually recommended after AFFS, but this increases the risk of rebound bone loss and vertebral fractures, especially after denosumab withdrawal.</li><li>Bridging strategies may help reduce rebound risk and include: Bisphosphonates, Raloxifene, Anabolic agents</li><li>Anabolic therapies, particularly teriparatide, can enhance fracture healing and reduce future fracture risk.&nbsp;</li><li><strong>Treatment sequencing is critical:</strong> A direct switch from denosumab to teriparatide may cause rapid cortical bone loss and increase fracture risk.</li><li>Careful, individualized treatment planning is essential to balance fracture healing, bone protection, and medication-related risks.</li></ul>

Ortho Update   Issue 1   Jan 2026

<ul><li><a href="#introduction">Introduction</a></li><li><a href="#diagnosis">Diagnosis of Osteoporosis</a></li><li><a href="#prevention">Prevention and screening</a></li><li><a href="#affs">Management of AFFs</a></li><li><a href="#osteoporosis">Osteoporosis management after AFFS - Therapeutic dilemma</a></li></ul>

AFOS 2025 Guidance on Atypical Femoral Fractures Associated with Osteoporosis Treatment

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