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.

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.

Reoperation rate and implant survivorship compared between cementless and cemented bipolar hemiarthroplasty in femoral neck fracture patients with chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is commonly associated with aging and disorders of mineral and bone metabolism. Femoral neck fracture (FNF) is one of the most common fractures among older adults with coexisting CKD, and bipolar hemiarthroplasty (BHA) is a preferred treatment. However, the optimal method of stem fixation has not been conclusively determined. Accordingly, this study aimed to investigate the reoperation rate and implant survivorship compared between cementless and cemented BHA in FNF patients with CKD. METHODS: A total of 183 FNF patients with moderate to severe CKD who underwent BHA during 2003 to 2019 were recruited and divided into either the cemented (CT group, n = 56) or cementless (CL group, 127) groups. Demographic data, preoperative laboratory investigations, preoperative radiographic outcomes, perioperative outcomes, and 90-day morbidity, mortality, and reoperation rates for any reason were recorded and compared between groups. Kaplan-Meier survival analysis was used to compare implant survivorship between the CT and CL groups. Cox proportional hazards regression model was used to identify independent risk factors for implant survivorship. RESULTS: There were no significant differences in patient characteristics or preoperative data between groups, except for Dorr's classification of proximal femoral geometry. The CT group had a significantly lower proportion of Dorr type A (p = 0.020), and a higher proportion of Dorr type C (p<0.001). The CT group also had significantly more intraoperative blood loss (p<0.01). No significant differences in morbidity or mortality were observed. The median follow-up time in the CT group and CL group was 22.6 months (range: 0-151) and 22.6 months (range 0-154), respectively (p = 0.607). The reoperation rate was 5.4% and 4.7% among CT and CL patients, respectively (p = 1.000). There was no significant difference in the mean survival time between the CT (139.5 ± 6.3 months, 95%CI: 127.1-151.8) and CL (142.5 ± 4.7 months, 95%CI: 133.2-151.7) groups (p = 0.880). Univariate and multivariate analyses revealed no independent risk factors for implant survivorship. CONCLUSION: The results of this study showed no significant differences in the reoperation rate or implant survivorship between cemented and cementless BHA for treating FNF in moderate to severe CKD patients. A well-designed larger and longer-term study is needed to confirm these results.

Impact of pre-exposure time bias in self-controlled case series when the event conditions the exposure: Hip/femur fracture and use of benzodiazepines as a case study.

BACKGROUND: In self-controlled case series (SCCS), the event should not condition the probability of subsequent exposure. If this assumption is not met, an important bias could take place. The association of hip/femur fracture (HFF) and use of benzodiazepines (BDZ) has a bidirectional causal relationship and can serve as case study to investigate the impact of this methodological issue. OBJECTIVES: To assess the magnitude of bias introduced in a SCCS when HFF conditions the posterior exposure to BDZ and explore ways to correct it. METHODS: Four thousand four hundred fifty cases of HFF who had at least one BZD prescription were selected from the primary care health record database BIFAP. Exposure to BZD was divided into non-use, current, recent, and past use. Conditional Poisson regression was used to estimate incidence rate ratios (IRRs) of HFF among current vs non-use/past, adjusted for age. To investigate possible event-exposure dependence, a pre-exposure time of different lengths (15, 30, and 60 days) was excluded from the reference category to evaluate the IRR. RESULTS: IRR of HHF for current use was 0.79 (0.72-0.86); removing 30 days, IRR was 1.43 (1.31-1.57). Removing 15 days, IRR was 1.29 (1.18-1.41), and removing 60 days, IRR was 1.56 (1.42-1.72). A pre-exposure period up to 182 days was necessary to remove such effect giving an IRR of 1.64 (1.48-1.81). CONCLUSIONS: HFF remarkably conditioned the use of BDZs resulting in seriously biased IRRs when this association was studied through a SCCS design. The use of pre-exposure periods of different lengths helped to correct this error.

Fluoxetine and Fractures After Stroke: Exploratory Analyses From the FOCUS Trial.

Background and Purpose- The FOCUS trial (Fluoxetine or Control Under Supervision) showed that fluoxetine did not improve modified Rankin Scale scores (mRS) but increased the risk of fractures. We aimed to describe the fractures, their impact on mRS and factors associated with fracture risk. Methods- A United Kingdom, multicenter, parallel-group, randomized, placebo-controlled trial. Patients ≥18 years with a clinical stroke and persisting deficit assessed 2 to 15 days after onset were eligible. Consenting patients were allocated fluoxetine 20 mg or matching placebo for 6 months. The primary outcome was the mRS at 6 months and secondary outcomes included fractures. Results- Sixty-five of 3127 (2.1%) patients had 67 fractures within 6 months of randomization; 43 assigned fluoxetine and 22 placebo. Fifty-nine (90.8%) had fallen and 26 (40%) had fractured their neck of femur. The effect of fluoxetine on mRS (common odds ratio =0.951) was not significantly altered by excluding fracture patients (common odds ratio =0.961). Cox proportional hazards modeling showed that only age >70 year (hazard ratio =1.97; 95% CI, 1.13-3.45; P=0.017), female sex (hazard ratio =2.13; 95% CI, 1.29-3.51; P=0.003), and fluoxetine (hazard ratio =2.00; 95% CI, 1.20-3.34; P=0.008) were independently associated with fractures. Conclusions- Most fractures resulted from falls. Although many fractures were serious, and likely to impair patients' function, the increased fracture risk did not explain the lack of observed effect of fluoxetine on mRS. Only increasing age, female sex, and fluoxetine were independent predictors of fractures. Clinical Trial Registration- URL: http://www.controlled-trials.com. Unique identifier: ISRCTN83290762.

Atypical incomplete femoral neck fracture in patients taking long-term bisphosphonate: Case report, a report of 2 cases.

RATIONALE: We present 2 cases of lateral incomplete impending fracture of the femoral neck without trauma in elderly patients taking long-term bisphosphonate (BP) treatment, and we defined it as atypical femoral neck fracture (AFNF). To the best of our knowledge, this is the first report on the follow-up results of AFNF. PATIENT CONCERNS: Patients in both cases had been taking BP drugs for a long time with osteoporosis. The duration of BP treatment was 6 years, and there was no history of repeated stresses. DIAGNOSES: All fractures were linear at the lateral aspect of the mid portion of the femoral neck, and the BMD of the femoral neck was -0.9, and -1.8, respectively. INTERVENTIONS: Internal fixation was performed in both cases (73 years, 68 years) using cannulated screws. OUTCOMES: In both patients who underwent screw fixation, the fracture line started to extend distally at 4 weeks and 2 weeks following surgery. In the 3-month follow-up image, the length of the fracture increased by 20.1 mm and 9.9 mm, respectively. There was a problem with active rehabilitation, and the possibility of revision was also found to be a burden in terms of mortality and cost in older patients. LESSONS: In the case of AFNF, guidelines for treatment should be set in consideration of the decreased bone healing, even when the fracture pattern is simple. Arthroplasty based on a wider indication may be worth considering.

Low-energy atypical femoral shaft and ipsilateral neck fracture: a rare association.

This reports a case of a low-energy ipsilateral femoral shaft and neck fracture in a 69-year-old woman with vitamin D deficiency, who was taking long-term steroids and bisphosphonates. This is a fracture more commonly associated with a high-energy trauma. However, with an ageing global population and an increasing prevalence of bone insufficiency, we predict the incidence of this presentation to increase. Long-term bisphosphonate therapy has been associated with bone insufficiency and an increased rate of delayed union, adding to the complexity of management in these patients. There is currently no consensus regarding the choice of optimal implant or fixation technique to treat this challenging fracture pattern. We discuss the considerations that led to our management approach of a non-overlapping dynamic hip screw and femoral shaft plate construct which achieved uneventful bone healing and a good functional outcome within the first year of follow-up.

A curious case of stress fracture in a transsexual athlete.

Femoral neck stress fractures in young healthy individuals are rare and occur in those who take part in physical training with repetitive loading and those with osteoporosis. Bone density is related to sex hormone status, which is artificially manipulated during gender reassignment. Conflicting evidence currently exists on the effect of cross sex hormone treatment on bone density, with no literature suggesting a link between hormone treatment in gender reassignment and stress fractures. Our aim is to highlight the potential risk of stress fractures amongst transsexual patients receiving cross sex hormones as part of gender reassignment. The patient presented with groin pain after competing in a running event. Despite a number of risk factors, there was a delay in diagnosis, which could have led to complications compromising outcome. Femoral neck stress fractures should be considered in the differential diagnosis of transsexual patients receiving hormone treatment with non-specific groin/thigh pain following exercise.

Bilateral non-traumatic hip fractures in a heavy smoker COPD patient on inhaled steroids.

INTRODUCTION: Bilateral proximal femoral fractures without trauma are very rare conditions. They have been reported in connection with osteoporosis, renal osteodystrophy, parathyroid disease, tumors, epileptic seizures, electroconvulsive therapy, and postirradiation. METHOD: We present a case of a 75-year-old man with bilateral hip fractures. No trauma, neurological, endocrinological disorder, or malignancy was reported in his history. He had a background of chronic obstructive pulmonary disease (COPD) and had been taking inhaled steroids (budesonide) 800 µg per day for 10 years. He was a heavy smoker with a smoking history of 120 packs/year. His complaints had initially started as pain on the left hip and groin and then had progressed to the right in 10 days. Plain x-rays of the pelvis showed left femoral neck and right subtrochanteric femoral fractures. Fixation with proximal femoral nail of the right hip and partial arthroplasty of the left hip was performed on the following day after his admission. Pathological examination revealed osteoporosis in bone samples from both hips. RESULT: COPD and osteoporosis have some common risk factors. Smoking, decreased exercise capacity, inhaled, or oral steroid therapy may increase osteoporosis and risk of bone fractures by decreasing bone mineral density. Non-traumatic femoral fractures may occur in patients on long-term inhaled steroid treatment for chronic airway diseases such as asthma and COPD. CONCLUSION: History of COPD with corticosteroid use may be used as a diagnostic tool to identify patients having osteoporosis. Preventive measures can be performed by monitoring high-risk patients with bone mineral densitometry, WHO fracture risk assessment tool (FRAX tool), serum calcium, and vitamin D levels to prevent bone fractures. Treating those patients with the lowest effective dose of corticosteroids should be targeted.

Atypical fractures, a biased perspective.

When stress fractures started to show up in the femurs of elderly ladies, it was soon evident that bisphosphonate use lay behind, and the absolute risk increase due to bisphosphonate use was reasonably well estimated already in 2008. Thereafter followed a period of confusion: the term atypical fracture was introduced, with a definition so vague that the true stress fractures tended to disappear in a cloud of ambiguity. This cast doubt on the association with bisphosphonates. The association was then re-established by large epidemiological studies based on radiographic adjudication. Atypical fractures are largely caused by bisphosphonates. With a correct indication, bisphosphonates prevent many more fractures than they cause, at least during the first years of use. With an incorrect indication they are likely to cause more harm than good.

Bisphosphonates and risk of subtrochanteric, femoral shaft, and atypical femur fracture: sensitivity and trim and fill studies.

OBJECTIVE: This study carried out sensitivity analysis and trim-fill analysis between bisphosphonates and subtrochanteric, femoral shaft, and atypical femur fracture. METHODS: A random-effects model was used finally. Sensitivity, trim and fill, and publication bias analyses were done. RESULTS: Under a random-effects model (I(2)=87.535), the Z-value=5.672, p-value of test of null<0.001. Bisphosphonate exposure was associated with an increased risk of atypical femur fracture (3.243 [95% CI 2.160-4.870]). When any study is removed, the remaining sensitivity analysis results are still significant. Trim and fill results show that two studies were missed. After filling them, a funnel plot of precision by log risk ratio was more symmetrical. CONCLUSION: This study suggests that (1) there is an increased risk of subtrochanteric, femoral shaft, and atypical femur fracture in bisphosphonate users; (2) any single study does not influence the total sensitivity; (3) two studies have been lost, theoretically.

Effective treatment of a steroid-induced femoral neck fracture nonunion with a once-weekly administration of teriparatide in a rheumatoid patient: a case report.

INTRODUCTION: Nonunion of femoral neck fractures frequently occurs in elderly patients. In patients with rheumatoid arthritis, reoperation rates after internal fixation of a displaced femoral neck fracture increase by up to 60 %. Revision surgery with arthroplasty is often preferred for nonunion of femoral neck fractures because there are few effective options for conservative treatment. Teriparatide (TPTD) is a human parathyroid hormone analog and the only anabolic drug for the treatment of severe osteoporosis. DISCUSSION: There are two types of treatment regimens using TPTD: a once-daily administration of recombinant type TPTD and a once-weekly administration of a chemically synthesized type. Although there have been some reports showing that the once-daily recombinant type TPTD was effective for nonunion treatment, the effect of a once-weekly administration of the chemically synthesized type of TPTD is unknown. This report shows the efficacy of the chemically synthesized TPTD for the treatment of femoral neck fracture nonunion in a patient with risk factors that include rheumatoid arthritis and steroid intake.

Pathological femoral fractures due to osteomalacia associated with adefovir dipivoxil treatment for hepatitis B: a case report.

We present a case of a 62-year-old man who underwent total hip arthroplasty for treatment of pathologic femoral neck fracture associated with adefovir dipivoxil-induced osteomalacia. He had a 13-month history of bone pain involving his shoulders, hips, and knee. He received adefovir dipivoxil for treatment of lamivudine-resistant hepatitis B virus infection for 5 years before the occurrence of femoral neck fracture. Orthopedic surgeons should be aware of osteomalacia and pathological hip fracture caused by drug-induced renal dysfunction, which results in Fanconi's syndrome. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1600344696739249.

Benefits and risks of bisphosphonate therapy for osteoporosis.

CONTEXT: There has been considerable concern recently in the scientific and lay media regarding the benefits vs. the risks of bisphosphonates for the treatment of osteoporosis. Risks include possible associations with osteonecrosis of the jaw (ONJ) and atypical femur fractures. In this perspective, we review the use of bisphosphonates for the treatment of osteoporosis, including an objective assessment of the risks vs. the benefits of these drugs. EVIDENCE ACQUISITION: Authors' knowledge of the field and results of focused literature searches are presented. EVIDENCE SYNTHESIS: Bisphosphonates have proven efficacy in the prevention of bone loss and in the reduction of fractures in postmenopausal women and men with established osteoporosis. Although bisphosphonates, at doses used to treat osteoporosis, may be associated with an increased risk of ONJ and atypical femur fractures, many more fractures are prevented by the use of these drugs compared to the relatively low risk of these complications. Although oral bisphosphonates are associated with upper gastrointestinal side effects and iv bisphosphonates with acute phase reactions, the association of bisphosphonate use with esophageal cancer and atrial fibrillation is not well supported by current data. CONCLUSIONS: Bisphosphonates have been proven to prevent fractures in patients with established osteoporosis or those who are at high risk of fracture. In contrast, the incidence of major complications associated with bisphosphonate use, such as ONJ and atypical femur fractures, is very low.

Unusual presentation of altered bone metabolism with long-term antiepileptic therapy: pathological fracture of neck of femur due to brown tumor at calcer.

The antiepileptic drugs are known to alter the bone metabolism and result in various range of pathological conditions (osteoporosis, osteomalacia, vitamin D deficiency, secondary hyperparathyroidism). These clinical conditions developed either due to direct effect of these therapeutic agents on bone or due to alteration in the homeostasis of other regulators of bone metabolism like serum calcium, vitamin D, and parathyroid hormone. Long-term therapy with antiepileptic agents results in higher incidence of pathological fracture, which is a consequence of either osteoporotic or osteomalasic (secondary to vitamin D deficiency) changes in bone produced by these drugs. Secondary hyperparathyroidism due to vitamin D deficiency following long-term polytherapy of antiepileptic drug ultimately leading to development of brown tumor and pathological fracture is very unusual.

Association of low-energy femoral fractures with prolonged bisphosphonate use: a case control study.

SUMMARY: Recent evidence has linked long-term bisphosphonate use with insufficiency fractures of the femur in postmenopausal women. In this case-control study, we have identified a significant association between a unique fracture of the femoral shaft, a transverse fracture in an area of thickened cortices, and long-term bisphosphonate use. Further studies are warranted. INTRODUCTION: Although clinical trials confirm the anti-fracture efficacy of bisphosphonates over 3-5 years, the long-term effects of bisphosphonate use on bone metabolism are unknown. Femoral insufficiency fractures in patients on prolonged treatment have been reported. METHODS: We performed a retrospective case-control study of postmenopausal women who presented with low-energy femoral fractures from 2000 to 2007. Forty-one subtrochanteric and femoral shaft fracture cases were identified and matched by age, race, and body mass index to one intertrochanteric and femoral neck fracture each. RESULTS: Bisphosphonate use was observed in 15 of the 41 subtrochanteric/shaft cases, compared to nine of the 82 intertrochanteric/femoral neck controls (Mantel-Haenszel odds ratio (OR), 4.44 [95% confidence interval (CI) 1.77-11.35]; P = 0.002). A common X-ray pattern was identified in ten of the 15 subtrochanteric/shaft cases on a bisphosphonate. This X-ray pattern was highly associated with bisphosphonate use (OR, 15.33 [95% CI 3.06-76.90]; P < 0.001). Duration of bisphosphonate use was longer in subtrochanteric/shaft cases compared to both hip fracture controls groups (P = 0.001). CONCLUSIONS: We found a significantly greater proportion of patients with subtrochanteric/shaft fractures to be on long-term bisphosphonates than intertrochanteric/femoral neck fractures. Bisphosphonate use was highly associated with a unique X-ray pattern. Further studies are warranted.

Bilateral femoral neck fractures in long-term steroid use for systemic lupus erythematosus and chronic lung disease.

Bilateral femoral neck fractures present a rare injury. Only one report to our knowledge was not related to an acute severe traumatic event, and developed years after pelvic irradiation. Chronic steroid use may severely decrease bone strength, thus increasing the risk for such an injury. Patients with chronic lung disease and chronic inflammatory conditions are frequently treated with steroids such as prednisone at doses that may exceed 2.5 mg a day for long durations. Fractures at vulnerable sites such as the femoral neck may then follow without any severe trauma. Awareness of the detrimental effect of chronic steroid consumption on bone morphology, and familiarity with treatment alternatives to improve bone mass is important to prevent such a severe injury. We describe two cases of bilateral femoral neck fractures in women who were treated for years with orally administered prednisone. The rarity of such an injury of bilateral hip fractures and the fact that neither of the patients sustained major trauma, strongly suggests that both cases were related to impaired bone metabolism due to the effect of prolonged steroid consumption. The biological effects of different roots of steroid administration on bone turnover, as well as several strategies that can be implemented by clinicians to treat and prevent steroid induced osteoporosis and fractures, are further clarified in this article.

[Multiple pathological fractures within the scope of DeToni-Debre-Fanconi syndrome after fumarate therapy in psoriasis]. / Multiple pathologische Frakturen im Rahmen eines DeToni-Debré-Fanconi-Syndroms nach Fumarattherapie bei Psoriasis.

We report about a rare case of a pathological fracture of the shank following earlier pathological fractures at other locations in a comparatively young female patient with no history of trauma. There were no known diseases other than psoriasis. The shank fracture was treated surgically by osteosynthesis. Osteoporosis, myeloma, or malignancy as causative factors of this fracture could be excluded. Scintigraphy showed an enhancement, especially at the extremities. Other than reactive bone growth, histological examination revealed no further aspects. Laboratory analysis indicated a massive lack of vitamin D3. After transferring the patient to the internal department of our hospital, long-term medication with fumaric acid was determined to be the reason for the osteomalacia of a Fanconi's syndrome. Three months after cessation of these medicaments and treatment with active vitamin D3 metabolites, the patient was free of complaints. The radiographs showed an essential improvement of the demineralization.