Atypical fractures of the lower extremities in two patients with rheumatoid arthritis: clinical presentations of presumed methotrexate osteopathy.

We present two patients who developed multiple lower limb stress fractures. Potential causes, such as osteoporosis, malignancies and disturbances in calcium metabolism were investigated. This led the physicians to consider whether methotrexate (MTX) exposure posed a risk of atypical fractures.The association between MTX and lower limb fractures has been described in at least 80 cases in the literature. Stress fractures associated with MTX treatment are atypical of osteoporosis and located in the lower extremities, most often the tibia. The limited data suggest that discontinuation of MTX may improve symptoms and chances of fracture healing, while antiresorptive or osteoanabolic therapies have not proven clinically efficient. It seems evident, however, that the benefits of MTX treatment in rheumatological disease clearly outweigh the risk of MTX osteopathy and related fractures.

Iron-induced Hypophosphatemic Osteomalacia-An Atypical Case of Bilateral Femoral Stress Fractures.

We present a case of a 61-year-old healthy man who had bilateral femoral neck insufficiency fractures attributed to repeated iron transfusions, causing iron-induced hypophosphatemic rickets, requiring surgical intervention. Atraumatic insufficiency fractures present a diagnostic dilemma in orthopaedics. Chronic fractures with no acute precipitating trigger can often go unrecognized until complete fracturing or displacement occurs. Early identification of the risk factors in conjunction with a comprehensive history, clinical examination, and imaging can potentially avoid these serious complications. Atraumatic femoral neck insufficiency fractures have been sporadically reported in the literature, often unilateral and attributed to the use of long-term bisphosphonates. Through this case, we elaborate on the relatively unknown link between iron transfusions and insufficiency fractures. This case highlights the importance of early detection and imaging of such fractures from an orthopaedic perspective.

An Interim Analysis of the First 102 Patients Treated in the Prospective Vertebral Augmentation Sacroplasty Fracture Registry.

PURPOSE: To evaluate the efficacy of sacroplasty for treating sacral insufficiency fractures, including the effect on pain relief, patient function and adverse event rates in an as-treated on-label prospective data registry. MATERIALS AND METHODS: Observational data including patient reported outcomes (PROs), patient characteristics, osteoporosis treatment, fracture duration, cause of sacral fractures and image guidance used for treatment were collected for patients undergoing sacroplasty. The PROs were collected at baseline then at one, three, and at six months following the procedure. The primary outcomes were pain as measured by the Numerical Rating Scale (NRS) and function as measured by the Roland Morris Disability Questionnaire (RMDQ). Secondary outcomes included adverse events, cement leakage, new neurologic events, readmissions and death. RESULTS: The interim results for the first 102 patients included significant pain reduction with mean pain improvement scores at six months decreasing from 7.8 to 0.9 (P < .001) and significant improvement in function with mean RMDQ scores improving from 17.7 to 5.2 (P < .001). Most procedures were performed under fluoroscopy (58%). There was cement leakage in 17.7% of the subjects but only one adverse event which was a new neurologic deficit related to cement extravasation. The readmission rate was 16% mostly due to additional back pain and fractures and there were no subject deaths. CONCLUSIONS: Sacroplasty with cement augmentation for acute, subacute and chronic painful sacral insufficiency fractures caused by osteoporosis or neoplastic disorders results in highly significant improvements in pain and function with very low rate of procedural related adverse events.

Bilateral calcaneal insufficiency fractures due to chronic carbamazepine use for trigeminal neuralgia: A case report.

Stress fractures of calcaneus are uncommon cause of heel pain. Stress fractures could be seen in risc groups such as metabolic diseases/medications causing poor bone quality and exposing repetitive microtrauma. Anti-epileptic drug (AED) use is related with poor bone quality and increased fracture risc. Although carbamazepine-induced stress fracture is a well-known entity and there are case reports in other bones such as the femoral neck, bilateral calcaneal insufficiency fractures is an extraordinary location. To the best of our knowledge, this is the first case reporting an insufficiency fracture involving calcaneus in the relevant literature. Due to the rarity of both conditions, we decided to present and discuss this patient. When patients receiving AED treatment present with heel pain without previous plantar fasciitis history or traumatic event, insufficiency fractures should be kept in mind. This case highlights the importance of screening adverse effect of CBZ on bone metabolism in patients with long CBZ use. We report here a 41-year-old lady suffering from bilateral heel pain without trauma history. Her complaining did not respond to analgesics and stretching exercises of plantar fascia. In her past medical history she reported ongoing carbamazepine (CBZ) use over 8 years for trigeminal neuralgia. She had had low bone mineral density; defined as osteopenia. Both calcaneus MRI revealed bilateral stress fractures of calcaneum. She had been advised immobilization for 6 weeks, vitamin D and calcium supplements. CBZ has been stopped by neurology specialist and she had undergone microvascular decompression surgery for intractable pain of trigeminal neuralgia. She is doing well with full recovery from heel pain and trigeminal neuralgia at the end of one year. CBZ use causes poor bone quality through vitamin D metabolism. Heel pain without traumatic event, objective findings of plantar fasciitis and calcaneal spur syndrome in an CBZ using patient insufficiency fracture of calcaneus should be remembered and evaluated rigorously.

Natural history of incomplete atypical femoral fractures in patients after a prolonged and variable course of bisphosphonate therapy-a long-term radiological follow-up.

Understanding the natural history of lateral femoral stress fractures helps to guide their management. Improvement in their radiographic characteristics is rare. Progression was generally sequential, most developing an incomplete fracture line before fracture displacement. Stopping bisphosphonates decreased the fracture rate, a feasible management option for lesions without incomplete fracture lines. INTRODUCTION: Retrospective study evaluating the natural history of lateral femoral stress fractures (FSF) by serial radiography over a variable period of time in a cohort of patients treated for some time with bisphosphonates for osteoporosis, whilst also identifying the fracture response in cases where bisphosphonates were discontinued. METHODS: The radiographs of 76 consecutive patients (92 femurs) with 161 FSF were reviewed to document their change over time. Femurs were classified into the following: A-normal, B-focal cortical thickening, C-dreaded black line and D-displaced fracture. Bisphosphonate history was recorded. RESULTS: 66.5% FSF showed group stability between the first and last radiographs: group B (79.1%), group C (45.7%). 28.6% progressed, mostly following an ordered sequence starting from group A, progressing to B, then C, before culminating in D. Progression rate was as follows: A-100% (11/11), B-18.3% (21/115), C-40% (14/35). Regression in FSF was uncommon-5.6% (8/161). 34.8% (32/92) sustained displaced fractures. Kaplan-Meier analysis showed statistically significant difference between the groups; median survival (95% CI): A-4189 (-), B-3383.0 (-), C-1807 (0.0-3788.6) and progression to displaced fracture when bisphosphonate had been stopped for at least 6 months. The group without recent bisphosphonates had a lower group progression rate (17.1%, 12/70). Nevertheless, 10.9% (5/46) progressed to displaced fracture. This group also had the highest proportion of stable (77.1%, 54/70) and regressive lesions (5.7%, 4/70). CONCLUSIONS: In FSF, there is natural progression from normal bone, to focal cortical thickening, to dreaded black line and eventually to displaced fracture. Most lesions persist, remaining static or progressing, especially if a dreaded black line is present and bisphosphonates are continued. Regression is uncommon and more frequent when bisphosphonates are discontinued. Despite stopping bisphosphonates, there remains a 10.9% risk of progression to displaced fracture.

Undisturbed local bone formation capacity in patients with atypical femoral fractures: a case series.

We excised the fracture site in 8 patients with incomplete atypical femoral fractures by drilling an 11-mm-diameter hole. New bone formation could be seen in the hole within a normal time frame. Delayed healing of these fractures might be unrelated to an impaired capacity to form bone. INTRODUCTION: Incomplete atypical femoral fractures (undisplaced cracks) heal slowly or not at all, and often progress to a complete fracture with minimal trauma. The impaired healing has been attributed to an impaired biologic healing capacity related to bisphosphonate use, or, alternatively, to the mechanical environment within the fracture crack. This study aimed to investigate the capacity for bone formation after resection of the fracture site. METHODS: Between 2008 and 2014, we recruited eight patients with incomplete atypical femoral fractures. All used oral bisphosphonates before the fracture for on average 8 years (range 4 to 15) and complained of thigh pain. The fractures were stabilized with reamed cephalomedullary nails. During surgery, the fracture site in the lateral cortex was resected with a cylindrical drill (diameter 11.5 mm). The cylindrical cortical defect allowed radiographic evaluation of new bone formation, and the patients were followed clinically and radiologically for 24 months (range 15 to 92). RESULTS: After 3 months, newly formed bone could be seen in the cortical defects in all patients. After 13-26 months, the previous defects showed continuous cortical bone. At final follow-up, all patients reported full recovery of pre-surgical complaints. No complications occurred and no reoperations were performed. CONCLUSIONS: New bone formation occurred within a time frame that appears normal for healing of cortical bone defects. This suggests that the capacity to form new bone is intact.

Signs of Insufficiency Fractures Overlooked in a Patient Receiving Chronic Bisphosphonate Therapy.

Chronic bisphosphonate therapy is associated with atypical fractures of the subtrochanteric and proximal femoral diaphyseal regions. Various radiologic imaging signs can identify bisphosphonate-associated stress fractures before they progress to complete fractures. Identifying patients who are at risk and modifying treatment can prevent these fractures from occurring. We present a case study of a patient taking bisphosphonate with 2 years of chronic pain, and characteristic clinical signs of bisphosphonate-associated incomplete stress fractures that went untreated until the patient suffered from a right subtrochanteric complete fracture. Our goal is to make physicians aware of the signs of insufficiency fractures associated with chronic bisphosphonate therapy such that appropriate clinical decisions are made to optimize the quality of patient care.

The advantages of tomosynthesis for evaluating bisphosphonate-related atypical femur fractures compared to radiography.

OBJECTIVE: To investigate the advantages of using tomosynthesis (TS) compared to radiographs in the detection, characterization, and follow-up of bisphosphonate-related atypical femur fractures (BP-AFF). SUBJECTS AND METHODS: Eight patients were identified retrospectively who underwent TS for radiographic findings suspicious for BP-AFF. Two radiologists independently interpreted 15 radiographs and 16 TS examinations, indicating the presence or absence of the following: (1) cortical "beaking" on radiographs, (2) radiolucent fracture line on radiographs, and (3) fracture lucency on TS corresponding to the site of radiographic abnormality. Radiation dose data were calculated for radiographs and TS using Monte Carlo analysis. RESULTS: There was agreement on 100 % of radiographs regarding the presence or absence of a cortical beak. Regarding the presence or absence of a fracture lucency, there was agreement on 100 % of TS examinations (Kappa = 1.0) and 73 % of radiographs (Kappa = 0.40 ± 0.24). For the 46 % of radiographs in which one or both radiologists did not visualize a fracture line, there was 100 % agreement for the presence of a fracture line on the corresponding TS. The interobserver agreement for fracture line detection was significantly higher for TS than for radiographs (p = 0.012). The effective radiation dose using TS was approximately 96 % lower compared to radiography. CONCLUSION: TS outperformed radiographs in the detection and characterization of BP-AFF. TS may also have advantages over radiography for BP-AFF follow-up through its unique ability to visualize fracture healing with lower effective radiation doses to the patient.

Tibial stress reaction presenting as bilateral shin pain in a man taking denosumab for giant cell tumor of the bone.

Prolonged bisphosphonate use has been associated with increased risk of atypical femoral fractures. Very few cases of atypical femoral fractures have been reported with denosumab. We report a case of bilateral tibial stress reactions in a 60-year-old man with no history of osteoporosis who was on prolonged high-dose denosumab for the treatment of giant cell tumor of bone. He presented with a 3-month history of pain in his bilateral shins worsening with activity and improving with rest. Although initial radiographs were unremarkable, he was found to have changes consistent with a stress reaction on magnetic resonance imaging of the distal tibia. To our knowledge, bilateral tibial stress reactions have not been previously reported with anti-resorptive therapies (neither bisphosphonates nor denosumab). Our case is intriguing in terms of the development of stress reactions as a precursor to stress fractures which may also relate to atypical fractures. Our case suggests a possible association between denosumab use and stress reactions. Of note the indication for denosumab in our case was for the treatment of giant cell tumor of bone where the Food and Drug Administration (FDA) approved dose is substantially higher than the FDA approved dose for osteoporosis treatment. Although rare, clinicians should consider the possibility of stress fractures in patients on anti-resorptive medications such as denosumab, especially when a patient presents with new onset thigh pain, hip pain or pain over an area affecting the long bones. Evaluation by imaging of affected areas should be pursued to enable early detection and intervention, as well as prevention of morbidity and associated ongoing risk to the patient.

Bilateral fatigue fractures of the bones of both crura in a patient with a history of abuse of alcohol and psychoactive substances treated with Ilizarov external fixator apparatus.

BACKGROUND: Fatigue (slow) fractures are a result of cyclic burden on the affected bones. At the same time, regeneration processes are disturbed or appropriate mechanical environment to promote healing is lacking. Fatigue fractures are classified into two types: stress fractures and deficiency fractures. The former occur as a result of excessive training in healthy individuals with normal bone structure, e.g. in sportsmen and soldiers. Deficiency-related fractures are most common in individuals with metabolic disorders that affect bone mineralization, such as osteomalacia or osteoporosis. CASE REPORT: The article presents a case of a 37-year-old male with fatigue fractures within both crura. During the interview, the patient reported the abuse of alcohol and benzodiazepines and the history of using other psychoactive substances. CONCLUSIONS: Fractures were treated using Ilizarov external fixator apparatus. Bone union was achieved after several months of external fixation.

Post-operative outcomes of atypical femoral subtrochanteric fracture in patients on bisphosphonate therapy.

Management of bisphosphonate-associated subtrochanteric fractures remains opinion- or consensus-based. There are limited data regarding the outcomes of this fracture. We retrospectively reviewed 33 consecutive female patients with a mean age of 67.5 years (47 to 91) who were treated surgically between May 2004 and October 2009. The mean follow-up was 21.7 months (0 to 53). Medical records and radiographs were reviewed to determine the post-operative ambulatory status, time to clinical and radiological union and post-fixation complications such as implant failure and need for second surgery. The predominant fixation method was with an extramedullary device in 23 patients. 25 (75%) patients were placed on wheelchair mobilisation or no weight-bearing initially. The mean time to full weight-bearing was 7.1 months (2.2 to 29.7). The mean time for fracture site pain to cease was 6.2 months (1.2 to 17.1). The mean time to radiological union was 10.0 months (2.2 to 27.5). Implant failure was seen in seven patients (23%, 95 confidence interval (CI) 11.8 to 40.9). Revision surgery was required in ten patients (33%, 95 CI 19.2 to 51.2). A large proportion of the patients required revision surgery and suffered implant failure. This fracture is associated with slow healing and prolonged post-operative immobility.

Clinician approach to diagnosis of stress fractures including bisphosphonate-associated fractures.

Stress fractures are repetitive strain injuries that occur in normal bones and in abnormal bones. Stress fractures share many features in common but differences depend on the status of the underlying bone. This review article for clinicians addresses aspects about stress fractures with particular respect to fatigue fractures, Looser zones of osteomalacia, atypical Looser zones, atypical femoral fractures associated with bisphosphonate therapy and stress fractures in Paget's disease of bone.

Recurrent bone fractures due to tenofovir-induced renal phosphate wasting.

A 42-y-old HIV-infected man suffered from several stress fractures due to tenofovir-induced proximal tubular injury. Laboratory examination revealed hypophosphatemia due to renal phosphate wasting. Therefore, more attention has to be paid to the monitoring of serum phosphate and alkaline phosphatase levels, since tenofovir-related nephrotoxicity increases the risk of osteomalacia.

Atypical bisphosphonate-associated subtrochanteric and femoral shaft stress fractures: diagnostic features on bone scan.

A 69-year-old woman presented with a spontaneous right subtrochanteric hip fracture. Pan-imaging following orthopedic repair failed to identify a primary malignancy to explain the presumed pathologic basis for this fracture. The patient then underwent bone scintigraphy and SPECT/CT which showed mild uptake in multifocal endosteal thickening of the lateral left femoral diaphysis, diagnostic of bisphosphonate-associated femoral shaft stress fractures, but no evidence of metastatic bone disease. Atypical bisphosphonate-associated subtrochanteric and femoral shaft stress fractures have a fairly specific appearance on bone scintigraphy, and nuclear medicine physicians should be aware of this relatively infrequent emerging pathology.

Steroid-induced stress fracture of medial tibial condyle: a case report.

Corticosteroid-induced stress fractures have been described, but such a presentation is rare in tibial condyle where osteonecrosis secondary to steroid use is more common. In this report we describe a case of stress fracture of medial tibial condyle secondary to corticosteroid (glucocorticoid) intake in a 47-year-old man. We discuss in detail the pathogenesis of this condition, and highlight the importance of various diagnostic modalities to avoid misdiagnosis of the condition. We also reiterate the importance of early diagnosis and prompt immobilization to prevent long-term morbidity in such cases.

Femoral canal obliteration secondary to prolonged alendronate use: a case report.

Insufficiency fractures secondary to prolonged alendronate use is due to inhibition of osteoclastic activity and suppressed bone turnover. Complications of fracture fixation include non-union, mal-union, and difficulty in intramedullary nail insertion. We report a technical challenge in intramedullary nailing of an obliterated femoral canal in a patient on long-term bisphosphonate treatment. The fracture site was explored. The medullary canal was re-created by drilling. Patience and caution during drilling and reaming are necessary to avoid iatrogenic fractures.

Frequency of incomplete atypical femoral fractures in asymptomatic patients on long-term bisphosphonate therapy.

OBJECTIVE: The purpose of our study was to determine the frequency and imaging features of atypical femoral fractures in a consecutive asymptomatic patient population on long-term bisphosphonate treatment and search for distinguishing clinical and laboratory parameters in the subset of patients with fractures. SUBJECTS AND METHODS: Two hundred femoral radiographs in 100 asymptomatic patients (93 women and seven men; age range, 47-94 years; mean age, 69.3 years) were prospectively reviewed by two radiologists. All patients had received bisphosphonate treatment for at least 3 years and had no history of pain or recent trauma. MRI studies were performed when a fracture was suspected on radiographs. Bone mineral density, serum calcium, albumin, 25-hydroxy vitamin D, intact parathyroid hormone (iPTH), serum C-telopeptide, and urine N-telopeptide values were obtained. RESULTS: Two of 100 patients (2%) had three insufficiency fractures. Both patients, 50 and 57 years old, were white, active, and had been receiving bisphosphonate therapy for 8 years. The patient with bilateral atypical femoral fractures showed typical features of bisphosphonate-related incomplete atypical femoral fractures. MRI confirmed the radiographic findings in both patients. The two patients with incomplete atypical femoral fractures were significantly younger than those without atypical femoral fractures. There were no significant differences among the fracture and nonfracture groups in terms of clinical or laboratory results, except for mean iPTH, which was significantly decreased in the fracture group. CONCLUSION: The 2% frequency of incomplete atypical femoral fractures in asymptomatic patients on long-term bisphosphonate therapy is higher than suggested in the literature. Aside from age and mean iPTH, there were no significant differences in clinical or laboratory data between the two groups.

Femoral stress fractures associated with long-term bisphosphonate treatment.

BACKGROUND: Recent studies have described unique clinical and radiographic characteristics of femoral stress fractures or low-energy fractures associated with long-term bisphosphonate therapy. However, it is unclear whether these fractures require subsequent surgery after the initial treatment. QUESTIONS/PURPOSES: We performed a cohort analysis of bisphosphonate-associated femoral stress fractures to (1) confirm the unique clinical and radiographic findings compared with existing literature, (2) determine whether any patients with completed fractures had no preexisting transverse stress fracture lines, (3) assess the need for additional surgical procedures, and (4) determine whether the hospital length of stay (LOS) differed for patients with prophylactic fixation of stress fractures versus fixation of completed fractures. METHODS: We retrospectively reviewed 16 patients with 24 diaphyseal and subtrochanteric femoral stress fractures (14) or low-energy fractures (10) who had been on bisphosphonates for 3 to 10 years. Data included demographics, symptoms, medication history, radiographic characteristics, treatment parameters, LOS, and outcome. Minimum followup was 9 months (average, 44.0 months; median, 31 months; range, 9-112 months). RESULTS: All patients had clinical and radiographic findings similar to those reported in the literature. Two of four patients sustained completed fractures after radiographs failed to reveal transverse lateral fracture lines. None of the 14 prophylactically treated impending fractures progressed or required additional surgery; however, in five of 10 femurs treated after fracture completion, six additional surgeries were performed. The average hospital LOS was shorter in patients who underwent prophylactic fixation (3.8 days) than in patients treated for completed fractures (5.6 days). CONCLUSIONS: Bisphosphonate-associated stress fractures and completed fractures are unique, possessing subtle characteristic radiographic features. Completed fractures may occur through the thickened bone in the absence of an appreciable transverse stress fracture line. Our observations suggest prophylactic reconstruction nail fixation may avoid fracture completion and may be associated with a shorter hospital LOS and less morbidity than treatment of completed fractures. LEVEL OF EVIDENCE: Level IV, diagnostic study. See the Guidelines for Authors for a complete description of levels of evidence.

Long-term bisphosphonate usage and subtrochanteric insufficiency fractures: a cause for concern?

For over a decade, bisphosphonate administration has evolved and become the cornerstone of the prevention and treatment of fragility fractures. Millions of post-menopausal women have relied on, and continue to depend on, the long-acting, bone density-maintaining pharmaceutical drug to prevent low-energy fractures. In return, we have seen the number of fragility fractures decrease, along with associated costs and emotional benefits. However, with any drug, there are often concerns with side effects and complications, and this unique drug class is seeing one such complication in atypical subtrochanteric femoral fracture, counterproductive to that which it was designed to prevent. This has created concern over long-term bisphosphonate administration and its potential link to these atypical fractures. There is controversial evidence surrounding such a definitive link, and no protocol for managing these fractures. This review offers the latest information regarding this rare but increasingly controversial adverse effect and its potential connection to one of the most successful forms of treatment that is available for the management of fragility fractures.