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.

Heroin-induced osteoporosis presented with bilateral femoral neck insufficiency fractures in a male adult: a case report.

BACKGROUND: Osteoporosis has been associated with several disorders; however, there have been only a limited number of reports on heroin-induced osteoporosis. We report a rare case presented with bilateral femoral neck insufficiency fractures without trauma history, caused by heroin-induced osteoporosis. We collect sufficient clinical data and further shed light on the potential mechanism of how heroin affects bone formation and decreases bone density. CASE PRESENTATION: A 55-year-old male patient with normal body mass index (BMI) suffered from bilateral hips pain gradually without trauma history. He had intravenous heroin addiction for more than 30 years. Radiography revealed bilateral femoral neck insufficiency fractures. Laboratory tests showed elevated alkaline phosphatase levels (365 U/L) and decreased inorganic phosphate (1.7 mg/dL), calcium (8.3 mg/dL), 25-(OH)D3 (20.3 ng/ml) and testosterone levels (2.12 ng/ml). Magnetic resonance imaging (MRI) revealed increased signals on STIR images over the sacral ala and bilateral proximal femur, and multiple band-like lesions at the vertebrae of the thoracic and lumbar spine. Bone densitometry revealed osteoporosis with a T score of minus 4.0. The screen for urine morphine was positive (> 1000 ng/ml). Through assessment of the patient, the diagnosis was insufficiency fractures of bilateral femoral neck caused by opioid-induced osteoporosis. After hemiarthroplasty, regular medication with vitamin D3 and calcium, and detoxification treatment, and the patient recovered well after 6 months of follow-up. CONCLUSION: The aim of this report is to highlight the laboratory and radiology findings in a case of osteoporosis caused by opioid addiction and discuss the potential pathway by which osteoporosis is induced by opioids. When an unusual osteoporosis presents with insufficiency fractures, heroin-induced osteoporosis should be considered.

Acetabular and sacral insufficiency fractures in a patient with a long-term history of Alendronate consumption; a case report.

BACKGROUND: Long-term Bisphosphonate consumption has been reported to be associated with the incidence of atypical or insufficiency fracture, particularly in the proximal femur. We observed a case of acetabular and sacral insufficiency fractures in a patient with a long-term history of Alendronate consumption. CASE PRESENTATION: A 62-year-old woman was admitted with a complaint of pain in right lower limb following low-energy trauma. The patient had a history of Alendronate consumption for more than 10 years. The bone scan revealed increased radiotracer uptake in the right side of the pelvic, proximal right femur, and sacroiliac joint. The radiographs showed type 1 sacrum fracture, acetabulum fracture with femur head protrusion into the pelvis, quadrilateral surface fracture, fracture of the right anterior column, and right superior and inferior pubic fracture. The patient was treated with total hip arthroplasty. CONCLUSION: This case highlights the concerns regarding long-term bisphosphonate therapy and its potential complications.

A rare side effect of methotrexate therapy: drug-induced osteopathy with multiple fractures of the lower limb.

Methotrexate is associated with bone lesions that are rare and, although presenting with a typical localisation to the lower extremities and appearing with a characteristic radiologic morphology, largely unknown and often misdiagnosed as osteoporotic insufficiency fractures. The correct and early diagnosis, however, is key for treatment and prevention of further osteopathology. Here, we present a patient with rheumatoid arthritis who developed multiple painful insufficiency fractures in the left foot (processus anterior calcanei, tuber calcanei) and in the right lower leg and foot (anterior and dorsal calcaneus and at the cuboid and distal tibia) during therapy with methotrexate, which were all misdiagnosed as osteoporotic. The fractures occurred between 8 months and 35 months after starting methotrexate. Discontinuation of methotrexate resulted in rapid pain relief and no further fractures have occurred. This case powerfully demonstrates the importance of raising awareness of methotrexate osteopathy in order to take appropriate therapeutic measures, including and perniciously discontinuing methotrexate.

A Scapular Spine Fracture Defined on the Basis of a Bisphosphonate: a Case Report and Review of the Literature.

Bisphosphonates are commonly used in the treatment of osteoporosis. Long-term use without drug holiday causes the risk of atypical fractures. Subtrochanteric and femoral stress fractures are among the frequently described complications. In our case report; a stress fracture of the scapular spine, a previously undescribed adverse effect of bisphosphonates, is presented. Key words: bisphosphonates, scapular spine, stress fracture, drug holiday.

Bisphosphonate-related atypical insufficiency fracture of the tibial plateau†:†A case report.

Objective : Only a few cases of insufficiency fractures of the tibial plateau following bisphosphonate use have been reported. The authors report a case with bisphosphonate (BP) -related atypical insufficiency fracture of tibial plateau, which developed delayed union. Patient : A 65-year-old Japanese woman presented with left knee pain without any trauma. She had a 5-year history of risedronate use for primary osteoporosis. Initial X-rays were unremarkable, but magnetic resonance imaging (MRI) confirmed an insufficiency fracture at the left tibial plateau at 3 weeks after the initial visit. Risedronate treatment was stopped because we diagnosed her with a BP-related atypical insufficiency fracture of the tibial plateau. She was treated with rest, a lateral wedge insole and protective weight-bearing with a T-cane for 3 months. Result : At 3-month follow-up, the patient still had a pain and a delayed healing on radiographs. Six months later, X-rays showed that the fracture site had a sclerotic change, but MRI revealed delayed union. At 8-month follow-up, the fracture was healed without any symptoms. Conclusion : All clinicians need to be aware of the delayed healing of atypical insufficiency fracture related with prolonged BP use. J. Med. Invest. 68 : 186-188, February, 2021.

Progression of atypical femur stress fracture after discontinuation of bisphosphonate therapy.

Atypical femur fracture (AFF) is an uncommon complication of long-term bisphosphonate use, but the risk declines substantially after treatment cessation. We report a case of a 70-year-old woman with osteopenia treated with alendronate for 9 years who presented with right mid-thigh pain and radiographic findings of focal lateral cortical thickening in the right mid-femur and lateral cortex irregularity in the proximal-mid left femur. Alendronate was discontinued, but she remained on estrogen for menopausal symptoms. Four years later, a horizontal linear translucent defect was seen in the right mid-femur area of cortical hypertrophy, consistent with an incomplete AFF. The patient underwent prophylactic intramedullary rodding of the right femur and estrogen was discontinued. Three years later (7 years after initial presentation), the cortical irregularities in the left femur were more prominent and three small horizontal linear translucent defects were now evident, consistent with early incomplete atypical fracture development. The patient also suffered a wrist fracture. She was treated with teriparatide for 1.5 years with resolution of the translucent defects in the left but not the right femur, although abnormal thickening of the lateral cortex persisted in both femurs. Our case demonstrates incomplete atypical femur fracture progression in a patient with long-term bisphosphonate exposure, even after treatment cessation. These findings highlight the importance of follow-up for patients who develop diaphyseal femur stress fractures and the potential for early healing with anabolic therapy. This case also demonstrates the challenge in managing older patients with incomplete AFF at risk for progression to complete AFF and osteoporotic fracture.

Emerging evidence that adaptive bone formation inhibition by non-steroidal anti-inflammatory drugs increases stress fracture risk.

There is mounting evidence suggesting that the commonly used analgesics, non-steroidal anti-inflammatory drugs (NSAIDs), may inhibit new bone formation with physical training and increase risk of stress fractures in physically active populations. Stress fractures are thought to occur when bones are subjected to repetitive mechanical loading, which can lead to a cycle of tissue microdamage, repair, and continued mechanical loading until fracture. Adaptive bone formation, particularly on the periosteal surface of long bones, is a concurrent adaptive response of bone to heightened mechanical loading that can improve the fatigue resistance of the skeletal structure, and therefore may play a critical role in offsetting the risk of stress fracture. Reports from animal studies suggest that NSAID administration may suppress this important adaptive response to mechanical loading. These observations have implications for populations such as endurance athletes and military recruits who are at risk of stress fracture and whose use of NSAIDs is widespread. However, results from human trials evaluating exercise and bone adaptation with NSAID consumption have been less conclusive. In this review, we identify knowledge gaps that must be addressed to further support NSAID-related guidelines intended for at-risk populations and individuals.

Clinical and Radiological Characterization of Patients with Immobilizing and Progressive Stress Fractures in Methotrexate Osteopathy.

Methotrexate (MTX) is one of the most commonly prescribed drugs for autoimmune rheumatic diseases. As there is no consensus on its negative effects on bone, the purpose of this investigation was to determine the clinical spectrum of patients with stress fractures due to long-term MTX treatment (i.e., MTX osteopathy). We have retrospectively analyzed data from 34 patients with MTX treatment, severe lower extremity pain and immobilization. MRI scans, bone turnover markers, bone mineral density (DXA) and bone microarchitecture (HR-pQCT) were evaluated. Stress fractures were also imaged with cone beam CT. While the time between clinical onset and diagnosis was prolonged (17.4 ± 8.6 months), the stress fractures had a pathognomonic appearance (i.e., band-/meander-shaped, along the growth plate) and were diagnosed in the distal tibia (53%), the calcaneus (53%), around the knee (62%) and at multiple sites (68%). Skeletal deterioration was expressed by osteoporosis (62%) along with dissociation of low bone formation and increased bone resorption. MTX treatment was discontinued in 27/34 patients, and a combined denosumab-teriparatide treatment initiated. Ten patients re-evaluated at follow-up (2.6 ± 1.5 years) had improved clinically in terms of successful remobilization. Taken together, our findings provide the first in-depth skeletal characterization of patients with pathognomonic stress fractures after long-term MTX treatment.

Multiple ipsilateral femoral stress fractures in a patient taking denosumab for osteoporosis-a case report.

This is the first report describing three ipsilateral femoral stress fractures in a patient taking denosumab. INTRODUCTION: Multiple reports of atypical femur fractures (AFF) in patients receiving denosumab have emerged recently. Denosumab is an anti-resorptive agent approved for treatment of osteoporosis. It is a human monoclonal antibody which blocks osteoclast activation, maturation, and function. METHODS: This is a case report of a 74-year-old female patient who sustained three stress fractures of her left femur. RESULTS: The patient healed her fractures after intramedullary nailing of the femur and was able to return to her activities. CONCLUSIONS: High index of suspicion is needed in any patient with osteoporosis on denosumab complaining of thigh or groin pain. Careful examination and radiographic studies of both femurs are warranted if AFF is discovered.

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.

Stress fractures in systemic lupus erythematosus after long-term MTX use successfully treated by MTX discontinuation and individualized bone-specific therapy.

We report the case of a 64-year-old woman with systemic lupus erythematosus (SLE) and recurrent bilateral stress fractures of the calcaneus due to long-term methotrexate (MTX) use. A detailed skeletal assessment pointed to osteoporomalacia with pronounced trabecular thinning and increased bone resorption. After years of unsuccessful treatment with bisphosphonates, a combined bone-specific denosumab-teriparatide treatment was initiated, and additional belimumab treatment was started to avoid intermittent steroid usage. As these measures did not lead to a significant improvement of the bone situation, MTX was eventually discontinued. This was followed by a rapid clinical improvement. In a follow-up MRI scan after 18 months, the stress fractures had almost disappeared. Furthermore, the bone density and microarchitecture markedly improved. In conclusion, this case demonstrates that MTX discontinuation/replacement in combination with an individualized and state-of-the-art bone-specific therapy is effective in SLE patients with stress fractures after long-term MTX use.

Nonsteroidal Anti-Inflammatory Drug Prescriptions Are Associated With Increased Stress Fracture Diagnosis in the US Army Population.

Stress fractures are common in military personnel and endurance athletes, and nonsteroidal anti-inflammatory drug (NSAID) use is widespread in these populations. NSAIDs inhibit prostaglandin synthesis, which blunts the anabolic response of bone to physical activity and could therefore increase risk of stress fracture. The objective of this study was to determine whether prescribed NSAIDs were associated with stress fracture diagnoses among US Army soldiers. We also aimed to establish whether acetaminophen, an analgesic alternative to NSAIDs, was associated with stress fracture risk. A nested case-control study was conducted using data from the Total Army Injury and Health Outcomes Database from 2002 to 2011 (n = 1,260,168). We identified soldiers with a diagnosis of stress fracture (n = 24,146) and selected 4 controls per case matched on length of military service (n = 96,584). We identified NSAID and acetaminophen prescriptions 180 to 30 days before injury (or match date). We also identified soldiers who participated in basic combat training (BCT), a 10-week period of heightened physical activity at the onset of Army service. Among these individuals, we identified 9088 cases and 36,878 matched controls. Conditional logistic regression was used to calculate incident rate ratios (RR) for stress fracture with adjustment for sex. NSAID prescription was associated with a 2.9-fold increase (RR = 2.9, 95% confidence interval [CI] 2.8-2.9) and acetaminophen prescription with a 2.1-fold increase (RR = 2.1, 95% CI 2.0-2.2) in stress fracture risk within the total Army population. The risk was more than 5-fold greater in soldiers prescribed NSAIDs (RR = 5.3, 95% CI 4.9-5.7) and more than 4-fold greater in soldiers prescribed acetaminophen (RR = 4.4, 95% CI 3.9-4.9) during BCT. Our results reveal an association between NSAID and acetaminophen prescriptions and stress fracture risk, particularly during periods of heightened physical activity. Prospective observational studies and randomized controlled trials are needed to support these findings before clinical recommendations can be made. © 2018 American Society for Bone and Mineral Research.

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.

High and pointed type of femoral localized reaction frequently extends to complete and incomplete atypical femoral fracture in patients with autoimmune diseases on long-term glucocorticoids and bisphosphonates.

Once a localized reaction (beaking) was detected, discontinuation of bisphosphonates (BPs) and switching to vitamin D supplementation or teriparatide therapy effectively improved its shape. When the localized reaction was high, of the pointed type, and/or accompanied by prodromal pain, the risks of complete and incomplete atypical femoral fracture increased and consideration of prophylactic fixation for such patients was required. INTRODUCTION: Femoral localized reaction (localized periosteal thickening of the lateral cortex, beaking) is reported to precede atypical femoral fractures (AFFs) and to develop in 8-10% of patients with autoimmune diseases taking BPs and glucocorticoids. The aims of the present study were to retrospectively investigate the shapes of localized reaction to consider how to manage the condition. METHODS: Twenty femora of 12 patients with autoimmune diseases who were on BPs and glucocorticoids exhibited femoral localized reaction. The heights of localized reaction were measured and the shapes classified as pointed, arched, and other. Localized reaction changes were divided into three categories: deterioration, no change, and improvement. A severe form of localized reaction was defined; this was associated with prodromal pain, de novo complete AFF, or incomplete AFF with a fracture line at the localized reaction. RESULTS: The mean height of localized reaction was 2.3 ± 0.8 mm (range, 1.0-3.7 mm) and the pointed type was 35%. Localized reaction was significantly higher (3.3 ± 0.8 vs. 2.1 ± 0.7 mm; p = 0.003) and the pointed type more common (78 vs. 27%; p = 0.035) in those with the severe form of localized reaction. Seven patients with localized reactions discontinued BPs just after localized reaction was detected, but five continued on BPs for 2 years. Localized reaction deterioration was more common in patients who continued than discontinued BPs (100 vs. 29%; p = 0.027). After 2 years, all patients had discontinued BPs and localized reaction did not deteriorate further in any patient. CONCLUSIONS: Once a localized reaction was detected, discontinuation of BPs and switching to vitamin D supplementation or teriparatide therapy effectively improved it. When the localized reaction was high, of the pointed type, and/or accompanied by prodromal pain, the risks of complete and incomplete AFF increased and consideration of prophylactic fixation for such patients was required.