scholarly journals Bilateral Atypical Femoral Fracture(AFF) After Teriparatide and Subsequent Anti-Resorptive Therapy: A Management Dilemma

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A184-A184
Author(s):  
Chandrika Reddy ◽  
Mohsen Zena ◽  
John C Gallagher ◽  
Robert R Recker ◽  
Robert J Anderson
Keyword(s):  
Femoral Fractures ◽  
Surgical Care ◽  
Mineral Density ◽  
Atypical Femoral Fractures ◽  
Dxa Scan ◽  
Increased Sensitivity ◽  
Healing Bone ◽  
Sclerostin Antibody ◽  
Dental Work

Abstract Introduction: Femoral fractures carry devastating morbidity for long term ambulation. Atypical femoral fractures (AFF) are uncommon, and bilateral AFFs are more rare with added post-fracture limitations. We report two patients with bilateral AFFs despite receiving teriparatide (TPTD). Case 1: A 72 y.o. Filipino lady with osteoporosis since late 1990 was treated with bisphosphonates (BP) intermittently over 25 years with drug holidays for dental work. She stopped alendronate in mid-2013 and continued raloxifene. She suffered a spontaneous left mid-femur AFF in June, 2015 that was treated with intramedullary (IM) rod and nailing. In July, 2015 she started TPTD 20 mcg daily for 23 months until May, 2017. Alendronate was restarted weekly. In December, 2018 she developed right thigh and hip prodromal pain without x-ray changes. In April, 2019 (46 months after the left AFF and 23 months after TPTD), she sustained a spontaneous right sub-trochanteric AFF. BP was stopped. After IM rod and nailing, she began a second course of TPTD. Case 2: 72 y.o Caucasian lady with osteoporosis since 2000 was treated with alendronate until April, 2006. She was switched to daily TPTD for 22 months from May, 2006 to March, 2008. Oral BP was resumed in April, 2008. She suffered a left AFF in November, 2009; BP was stopped in March, 2010. In July, 2010 she sustained a right AFF (9 months after the left AFF and 28 months post-TPTD). Each spontaneous AFF occurred after prodromal pain, and each was treated with IM rod placement with nailing. She received BP infusion in 2011 and TPTD from March, 2012 to March, 2014. DXA scan in 2020 showed lumbar spine osteopenia. She currently takes calcium and Vit D supplementation. Discussion: TPTD is reported as a potential treatment for enhancing AFF healing, bone mineral density and pain resolution. The expectation is that it might prevent contralateral AFF. No randomized studies of prevention of AFF with TPTD exist. Available reports show variable results. Prolonged presence of BP in bone may contribute to this variation. We identified 7 reported AFF patients treated with TPTD who then developed a contralateral AFF. We found 2 patients with new AFF after TPTD as in our Case 2. In all cases there was previous exposure to BP. Perhaps the 28–30% risk of a contralateral AFF within 4 years in the setting of BP is irremediable. Conclusion: TPTD increases healing of AFF in some reports, but prevention of an initial or further AFF has not been well documented. Our 2 patients and 9 others reported suggest a possible subset with increased sensitivity to the effect of BP and increased AFF risk. The best choice after TPTD is unclear, but it may include permanent removal of anti-resorptive agents. The anti-sclerostin antibody romosozumab also has been associated with AFF. Choices are limited for these patients other than excellent surgical care, adequate calcium/vitamin D intake, and periodic imaging as symptoms dictate.

scholarly journals THERAPY OF ENDOCRINE DISEASE: Denosumab vs bisphosphonates for the treatment of postmenopausal osteoporosis

2018 ◽  
Vol 179 (1) ◽  
pp. R31-R45 ◽  
Author(s):  
Athanasios D Anastasilakis ◽  
Stergios A Polyzos ◽  
Polyzois Makras
Keyword(s):  
Fracture Risk ◽  
Femoral Fractures ◽  
Osteonecrosis Of The Jaw ◽  
Mineral Density ◽  
Atypical Femoral Fractures ◽  
Term Administration ◽  
Treatment Naïve ◽  
Fracture Risk Reduction ◽  
Pretreated Patients

The most widely used medications for the treatment of osteoporosis are currently bisphosphonates (BPs) and denosumab (Dmab). Both are antiresorptives, thus targeting the osteoclast and inhibiting bone resorption. Dmab achieves greater suppression of bone turnover and greater increases of bone mineral density (BMD) at all skeletal sites, both in naïve and pretreated patients. No superiority on fracture risk reduction has been documented so far. In long-term administration, BPs reach a plateau in BMD response after 2–3 years, especially at the hip, while BMD increases progressively for as long as Dmab is administered. Both BPs and Dmab are generally considered safe, although they have been correlated to rare adverse events, such as osteonecrosis of the jaw and atypical femoral fractures. Dmab should be preferred in patients with impaired renal function. BPs are embedded in the bone, from which they are slowly released during bone remodeling, therefore continuing to act for years after their discontinuation. In contrast, Dmab discontinuation fully and rapidly reverses its effects on bone markers and BMD and increases the risk for fractures; therefore, Dmab discontinuation should be discouraged, especially in previously treatment-naïve patients, regardless of the conventional fracture risk. In case of discontinuation, other treatment, mainly BPs, should immediately follow, although the optimal sequential treatment strategy is yet to be defined. Combination of teriparatide with Dmab or zoledronic acid, but not alendronate, provides increased BMD gains at all sites. In conclusion, both BPs and Dmab are safe and efficient therapeutic options although their particularities should be carefully considered in an individual basis.

scholarly journals Duration of Bisphosphonate Drug Holidays in Osteoporosis Patients: A Narrative Review of the Evidence and Considerations for Decision-Making

2021 ◽  
Vol 10 (5) ◽  
pp. 1140
Author(s):  
Kaleen N. Hayes ◽  
Elizabeth M. Winter ◽  
Suzanne M. Cadarette ◽  
Andrea M. Burden
Keyword(s):  
Surrogate Marker ◽  
Femoral Fractures ◽  
Osteonecrosis Of The Jaw ◽  
Bisphosphonate Therapy ◽  
Narrative Review ◽  
Drug Holiday ◽  
Future Research ◽  
Mineral Density ◽  
First Line Therapy

Bisphosphonates are first-line therapy for osteoporosis, with alendronate, risedronate, and zoledronate as the main treatments used globally. After one year of therapy, bisphosphonates are retained in bone for extended periods with extended anti-fracture effects after discontinuation. Due to this continued fracture protection and the potential for rare adverse events associated with long-term use (atypical femoral fractures and osteonecrosis of the jaw), a drug holiday of two to three years is recommended for most patients after long-term bisphosphonate therapy. The recommendation for a drug holiday up to three years is derived primarily from extensions of pivotal trials with alendronate and zoledronate and select surrogate marker studies. However, certain factors may modify the duration of bisphosphonate effects on a drug holiday and warrant consideration when determining an appropriate time off-therapy. In this narrative review, we recall what is currently known about drug holidays and discuss what we believe to be the primary considerations and areas for future research regarding drug holiday duration: total bisphosphonate exposure, type of bisphosphonate used, bone mineral density and falls risk, and patient sex and body weight.

scholarly journals Sequential treatment with teriparatide and strontium ranelate in a postmenopausal woman with atypical femoral fractures after long-term bisphosphonate administration

HORMONES ◽  
2013 ◽  
Vol 12 (4) ◽  
pp. 591-597 ◽  
Author(s):  
Kalliopi Lampropoulou-Adamidou ◽  
Symeon Tournis ◽  
Alexia Balanika ◽  
Ioulia Antoniou ◽  
Ioannis Stathopoulos ◽  
...  
Keyword(s):  
Postmenopausal Woman ◽  
Strontium Ranelate ◽  
Femoral Fractures ◽  
Sequential Treatment ◽  
Atypical Femoral Fractures

scholarly journals Nontraumatic bilateral atypical femoral fractures associated with long-term alendronate therapy

2020 ◽  
Vol 9 (11) ◽  
pp. 1737
Author(s):  
Olayinka A. Ogundipe
Keyword(s):  
Femoral Fractures ◽  
Case Definition ◽  
Term Therapy ◽  
Caucasian Woman ◽  
X Rays ◽  
Medication History ◽  
Mineral Research ◽  
Atypical Femoral Fractures ◽  
Femur Fractures

Alendronate is a bisphosphonate commonly used in the treatment of post-menopausal and steroid-associated osteoporosis. Bisphosphonates have an evidence base for reducing the occurrence of typical osteoporotic fractures. However, there has been growing recognition of a correlation with the use of long-term therapy with bisphosphonates, and rare occurrence of atypical femoral fractures (AFFs). This report describes a 72-year-old caucasian woman presenting with evolving groin and thigh pains of two weeks duration. Plain X-rays noted features compatible with bilateral impending femoral subtrochanteric fractures. She had been taking oral alendronate 70mg weekly for ten consecutive years as treatment for osteoporosis. Based on the medication history, the absence of preceding trauma or a fall, and the presence of supportive radiological findings, the diagnosis was made of impending bilateral proximal femur fractures secondary to long-term bisphosphonate therapy. The alendronate was discontinued, and the patient managed with two planned successive surgeries involving the insertion of intertrochanteric antegrade nails (inter-TAN) to both femurs. Following a period of rehabilitation, she was successfully discharged home. Some pharmacokinetic and pharmacodynamic considerations of bisphosphonates are discussed. The write-up presents a brief literature review of AFFs. The index report is further reviewed in relation to the American society for bone and mineral research (ASBMR) task force’s recommended case definition of what constitutes AFFs. The discussion concludes with the application of two previously validated causality assessment systems (CAS). In this instance, both CAS indicated a ‘probable’ classification for the adverse drug reaction (ADR) to prolonged usage of oral alendronate.

Medication-Induced Musculoskeletal Changes

2019 ◽  
pp. 322-326
Author(s):  
Winnie A. Mar
Keyword(s):  
Musculoskeletal System ◽  
Gold Standard ◽  
Imaging Modality ◽  
Femoral Fractures ◽  
Osteonecrosis Of The Jaw ◽  
Bisphosphonate Therapy ◽  
Atypical Femoral Fractures ◽  
Osteoblastic Activity ◽  
Induced Changes

Chapter 117 discusses common medication-induced changes of the musculoskeletal system. The effect of corticosteroids on the musculoskeletal system, including osteoporosis and osteonecrosis, is discussed. Corticosteroids decrease osteoblastic activity, stimulate bone resorption, and decrease intestinal absorption of calcium. Complications of bisphosphonate therapy such as atypical femoral fractures and osteonecrosis of the jaw are reviewed. Myopathies and tendon pathologies are briefly discussed, as well as bony changes potentially seen with long-term voriconazole treatment. For osteoporosis, DXA scan is the gold standard, whereas radiography is usually the first imaging modality performed in patients on voriconazole therapy who present with pain.

Risk factors for development of atypical femoral fractures in patients on long-term oral bisphosphonate therapy

Bone ◽  
2013 ◽  
Vol 56 (2) ◽  
pp. 426-431 ◽  
Author(s):  
Paola Franceschetti ◽  
Marta Bondanelli ◽  
Gaetano Caruso ◽  
Maria Rosaria Ambrosio ◽  
Vincenzo Lorusso ◽  
...  
Keyword(s):  
Risk Factors ◽  
Femoral Fractures ◽  
Bisphosphonate Therapy ◽  
Atypical Femoral Fractures ◽  
Oral Bisphosphonate

scholarly journals MANAGEMENT OF ENDOCRINE DISEASE: Atypical femoral fractures: risks and benefits of long-term treatment of osteoporosis with anti-resorptive therapy

2018 ◽  
Vol 178 (3) ◽  
pp. R81-R87 ◽  
Author(s):  
Robert A Adler
Keyword(s):  
Osteoporotic Fracture ◽  
Femoral Fractures ◽  
Osteoporosis Treatment ◽  
Term Treatment ◽  
Atypical Femoral Fractures ◽  
Treatment Of Osteoporosis ◽  
Endocrine Disease ◽  
Long Term Treatment ◽  
Term Management

Modern osteoporosis treatment began in the mid-1990s with the approval of amino-bisphosphonates, anti-resorptive agents that have been shown to decrease osteoporotic fracture risk by about half. In 2005, the first cases of atypical femoral fractures (AFF), occurring in the shaft of the femur, were reported. Since then, more cases have been found, leading to great concern among patients and a dramatic decrease in bisphosphonate prescribing. The pathogenesis and incidence of AFF are reviewed herein. Management and an approach to prevention or early detection of AFF are also provided. Denosumab, a more recently approved anti-resorptive medication has also been associated with AFF. Long-term management of osteoporosis and prevention of fracture are challenging in light of this serious but uncommon side effect, yet with an aging population osteoporotic fracture is destined to increase in frequency.

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