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.

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.

Sensitivity and specificity of radiographic characteristics in atypical femoral fractures.

Using the American Society for Bone and Mineral Research Task Force case definition for atypical femoral fractures, sensitivity and specificity of radiographic fracture characteristics were calculated. Fracture pattern was the most sensitive and specific characteristic. This suggests that some characteristics should be weighted more heavily when identifying these fractures. INTRODUCTION: To estimate the sensitivity and specificity of each radiographic criterion in the 2013 ASBMR atypical femoral fracture (AFF) case definition for distinguishing AFF from other subtrochanteric/diaphyseal fractures (non-AFF) among women enrolled in a large integrated health care organization. METHODS: Radiographs from 55 physician-confirmed AFFs and a sample of 39 non-AFFs were reviewed by four independent expert reviewers representing four medical specialties. One image per fracture was selected for review. Using a standardized data collection tool, based on the 2013 AFF case definition, reviewers indicated the presence or absence of the following characteristics viewable on radiograph: fracture pattern, comminution, periosteal and/or endosteal thickening, and cortical thickening. Sensitivity and specificity for each characteristic was calculated for each reviewer and summarized across reviewers with the mean and range. Agreement across reviewers was quantified using Fleiss's kappa (FK) statistic. RESULTS: The most sensitive factors distinguishing AFF from non-AFF were lateral cortex transverse fracture pattern (mean 93.6 %, range 85.5-98.2 %), medial cortex transverse or oblique fracture pattern (mean 84.1 %, range 72.7-98.2 %), and minimal/non-comminution (mean 93.2 %, range 89.1-98.2 %). Specificity was the greatest for lateral cortex transverse fracture pattern (mean 95.5 %, range 92.3-97.4 %). Agreement across reviewers was the highest for lateral cortex transverse fracture pattern (FK 0.83) and incomplete fracture through the lateral cortex only (FK 0.80). CONCLUSION: Lateral cortex transverse fracture pattern was the most sensitive and specific characteristic and the most highly agreed upon across reviewers. Other characteristics were less readily agreed upon across reviewers. Measurement of discrete combinations of individual characteristics may enhance sensitivity and/or specificity.

[Three patients with a fracture during methotrexate use, possibly due to methotrexate osteopathy]. / Drie patiënten met een botfractuur tijdens het gebruik van methotrexaat, mogelijk door methotrexaatosteopathie.

Three female patients, aged 76, 64 and 74 years old, who were treated with low-dose methotrexate due to an inflammatory joint disorder, developed severe pain in a lower extremity. The pain increased on weight bearing and could not be explained by arthritis. Conventional x-ray investigation showed a fracture in the second patient. In the other two patients insufficiency fractures were visualized by MRI and bone scan. Because methotrexate osteopathy was suspected, treatment with methotrexate was stopped. All three patients made a rapid recovery after discontinuation. Methotrexate osteopathy is characterized by pain, osteoporosis and microfractures, and was first reported in children treated with high-dose methotrexate for a malignancy. Similar clinical features are reported in the literature in patients with chronic joint inflammation treated with low-dose methotrexate. The causal relationship between the insufficiency fractures and the use of methotrexate is still under debate. Although the clinical picture fits with methotrexate osteopathy, these patients often also have other risk factors for osteoporotic insufficiency fractures.

Long-term magnesium sulfate tocolysis and maternal osteoporosis in a triplet pregnancy: a case report.

Prolonged infusion of magnesium sulfate has been used for the treatment of refractory preterm labor. Long-term magnesium sulfate tocolytic therapy either alone or in combination with other tocolytic agents has been reported to be safe and effective with minimal maternal side effects. There has been only one previous report of a disturbance in maternal calcium homeostasis, which included decreased distal radius bone density and hypercalciuria as a result of prolonged magnesium sulfate infusion. This article reports the first case of bilateral fracture of the calcanei in the postpartum period secondary to osteoporosis associated with prolonged magnesium sulfate tocolysis and bed rest. A 35-year-old white female with a triplet pregnancy of 25 weeks' gestation was admitted in preterm labor. Bed rest, intravenous magnesium sulfate tocolysis, and intermittent subcutaneous terbutaline were necessary to maintain uterine quiescence for 65 days. The patient received weekly betamethasone for 6 weeks for the acceleration of fetal lung maturation. Daily prenatal multivitamins and low-dose subcutaneous heparin for thromboprophylaxis were given. Efforts at tocolysis were ultimately not successful and the patient underwent a cesarean section delivery at 34 2/7 weeks' gestation. The patient's postoperative course was complicated by osteoporosis and bilateral stress fractures of the calcanei. This case report demonstrates that stress fractures secondary to osteoporosis may be associated with prolonged magnesium sulfate therapy and bed rest in higher order multiple pregnancy. Other possible contributing factors to osteoporosis include heparin thromboprophylaxis and suboptimal calcium supplementation. Therefore, in circumstances of prolonged bed rest and magnesium sulfate tocolysis, additional daily calcium supplementation would be well advised.

Methotrexate osteopathy in long-term, low-dose methotrexate treatment for psoriasis and rheumatoid arthritis.

BACKGROUND: In dermatology and rheumatology, methotrexate is frequently prescribed in low dosages per week; in oncology, high dosages per week are prescribed. Methotrexate osteopathy was first reported in children with leukemia treated with high doses of methotrexate. In animal studies, low doses of methotrexate proved to have an adverse effect on bone metabolism, especially on osteoblast activity. OBSERVATIONS: Methotrexate osteopathy is a relatively unknown complication of low-dose methotrexate treatment. We describe three patients treated with low-dose oral methotrexate in whom signs and symptoms were present that were similar to those found in children treated with high doses of methotrexate. All three patients had a triad of severe pain localized in the distal tibiae, osteoporosis, and compression fractures of the distal tibia, which could be identified with radiographs, technetium Tc 99m scanning, and magnetic resonance imaging. CONCLUSIONS: Methotrexate osteopathy can occur in patients treated with low doses of methotrexate, even over a short period of time. As pain is localized in the distal tibia, it is easily misdiagnosed as psoriatic arthritis of the ankle, but the diagnosis can be correctly made by careful investigation and use of imaging techniques. The only therapy is withdrawal of methotrexate. It is important that more physicians become aware of this side effect of methotrexate therapy, which can occur along with arthritic symptoms.

[Stress fractures during fluoride therapy. Physiopathological value of histomorphometry]. / Fractures de contrainte sous fluorothérapie. Intérêt physiopathologique de l'histomorphométrie.

Bone histomorphometry was carried out in 11 women, aged 53 to 80 (mean = 69.6), treated with fluoride for vertebral osteoporosis for more than 6 months and having suffered one or more stress fractures (1 to 4 sites, mean = 1.7 sites) during that time. Classical contraindications were complied with in all cases but 2 patients did not have any combined calcium supplement. In 6 cases, histomorphometry showed no sign (notably hyperosteoidosis) of the effects of fluoride on bone. Bone trabecular volume was markedly below the fracture threshold in 4 patients. This group refractory to fluoride included the two patients who had received no calcium supplement. In 5 cases, histomorphometry showed hyperosteoidosis of normal or low thickness, with a normal mineralisation rate, reflecting the effects of fluoride on bone. However, bone trabecular volume remained below the fracture threshold in all cases. In all 11 cases, bone structure studied in polarised light was lamellar and there was no increase in cortical porosity. These results suggest that the imputability to fluoride of peripheral bone accidents must be viewed very relatively (the persistence of an insufficient bone trabecular volume being the feature usually found) or, at any event, that its possible iatrogenic effect is not linked to bone remoulding abnormalities.

Stress fractures of the lower limbs in osteoporotic patients treated with fluoride.

We report clinical and bone morphometric findings in 18 osteoporotic patients who experienced stress fractures during fluoride therapy. Patients were treated with either sodium fluoride (n = 15), or sodium monofluorophosphate (n = 3). Oral calcium supplementation was given in 11 patients, and vitamin D in 13. Stress fractures occurred after 17.1 +/- 10.3 months of therapy (range: 5-41 months). Atraumatic sudden pain in a lower limb bone extremity, normal initial roentgenogram, high 99technetium uptake on early bone scan, and a 3 to 4 week delay in linear bone condensation area at the same site were characteristics of stress fracture. The most frequent sites were the tibial metaphysis (n = 13), femoral neck (n = 10), and calcaneus (n = 4). Biochemical data showed increased plasma alkaline phosphatase levels in 11 patients, and mild renal failure in 2. Bone histomorphometry was performed on an iliac crest specimen in 10 patients at the time of the stress fracture. Trabecular bone volume was normal, and formation parameters were increased. Features of osteomalacia were encountered in only 2 patients with decreased renal function. Trabecular resorption was increased, as assessed by the osteoclastic surface (1.01 +/- 1.15% bone surface), and the number of osteoclasts (0.44 +/- 0.49 per mm2 bone section). The clinical course was favorable in all patients who stopped fluoride, although 5 patients who continued the treatment had either completion of femoral neck stress fractures to hip fractures (n = 2), or recurrent stress fractures (n = 2), or both (n = 1). Fluoride appears to be a key factor in the pathogenesis of stress fractures, and may be associated with increased trabecular resorption in some treated patients.

Spontaneous hip fractures in fluoride-treated patients: potential causative factors.

Spontaneous fractures were reported to be rare (less than 1%) in 1664 hospital admissions for hip fracture in the 1950s in Sweden. We report 11 fluoride-treated postmenopausal patients who developed spontaneous fractures of the femoral necks, all subcapital initially. In 7 patients who continued treatment there were later femoral neck or shaft fractures; in 6, these were bilateral (one followed a fall). In all there were 19 spontaneous fractures: 5 were asymptomatic, including 2 with deformity; 12 fractures required surgery. Five were incomplete (stress) fractures. All were treated with supplementary calcium 1 g daily; 10 had vitamin D supplementation. In all patients where the timing was known, the initial and subsequent fractures were preceded by, or associated with increased bone turnover as measured by plasma alkaline phosphatase (pAlP) (i.e., they were all "good responders"). Two had pretreatment hip fractures following falls. We compared these 11 (Group 1) and another identically treated group of 14 patients (Group 2), without spontaneous femoral fractures and not different in mean age, pretreatment vertebral fractures, years since menopause, fluoride dosage, and plasma creatinine. Group 1 had a lower (p less than 0.05) index of cortical bone in the femoral neck, as assessed by the ratio "calcar width/femoral neck minimum width." The 6 biopsied fluorotic patients from Group 1 had a higher (p less than 0.05) bone fluoride content than the 4 biopsied fluorotic patients from Group 2. Furthermore, histological cortical features of thinning, increased porosity, and advanced tunneling resorption characterized Group 1 posttreatment biopsies. There were no significant differences in peak pAlP responses in the two groups. Mild asymptomatic vitamin D excess may have been a contributing factor in three Group 1 patients. Two further treatment groups have been studied more recently by forearm single-photon absorptiometry (SPA) at two sites; a cyclic NaF group (Group 3) and a calcium +/- vitamin D group (Group 4). Neither showed significant changes in forearm cortical bone density on treatment for 2 and 1.5 years, respectively, but Group 3 showed a significant increase in density at an ultradistal (60% trabecular) site. The pAlP response in Group 3 was significantly less than in Group 1. Spontaneous femoral neck or shaft fractures did not occur in either Groups 3 or 4. Therefore, we recommend: (1) Avoidance of sodium fluoride (NaF) treatment if pretreatment femoral fracture or thin femoral neck cortices exist.(ABSTRACT TRUNCATED AT 400 WORDS)