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.

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.

Antiresorptive-associated spontaneous fractures of both tibiae, followed by an atypical femur fracture during the sequential treatment with alendronate, denosumab then teriparatide.

A 35-year-old man with juvenile idiopathic arthritis since childhood presented with bilateral atypical tibial fractures, followed by a later, single atypical fracture of the femur. The fractures were associated with 6 years of oral alendronate treatment immediately followed by subcutaneous denosumab therapy and later teriparatide therapy for osteoporosis. Atypical fractures are known to occur in the femur following bisphosphonate therapy; however, there are only a few documented cases of atypical fractures in the tibia. Our case highlights a rare but serious complication of a commonly prescribed antiresorptive agent. It also shows that teriparatide, while helpful in increasing bone mass, does not fully prevent the development of atypical fractures. Careful investigation should be considered in patients on long-term antiresorptive therapy presenting with bony tenderness to exclude an atypical fracture.

Atypical fracture of the tibial diaphysis associated with bisphosphonate therapy: a case report.

Atypical subtrochanteric femoral shaft fractures (AFFs) have recently emerged as a potential long-term complication of bisphosphonate therapy. In 2010, the American Society for Bone and Mineral Research (ASBMR) Task Force published a definition for AFF consisting of 5 major and 7 minor features. Little attention has so far been paid to the possibility that bisphosphonate-associated atypical fractures may also involve the diaphysis of other long bones. We report here the case of a patient on long-term bisphosphonate therapy who presented a diaphyseal tibial insufficiency fracture fulfilling all the major criteria (except for the location), and a number of the minor criteria of an atypical fracture. Our case report suggests the need for greater awareness of the possibility of atypical fractures at other sites, particularly in weight-bearing long bones other than the femur, and suggests that long-term bisphosphonate therapy may also contribute to the occurrence of these atypical fractures.

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.

Suplementação de vitamina C não acelera o processo de consolidação de fratura da tíbia em ratos / Supplementary vitamin C does not accelerate bone healing in a rat tibia fracture model

OBJETIVO: Investigar a função da suplementação de ácido ascórbico na consolidação de fraturas da tíbia de ratos. MÉTODOS: Trinta ratos Wistar machos foram aleatoriamente divididos nos grupos Vitamina C (Grupo A) e sham (Grupo B), com 15 ratos em cada grupo. Ao grupo A foram administrados 200mg/kg de ácido ascórbico por dia intraperitonialmente e ao grupo B,5ml/kg de soro fisiológico intraperitonialmente uma vez ao dia. Os animais foram separados em duplas e colocados em gaiolas, com água e ração padrão ad libitum. As fraturas foram produzidas manualmente, não foram estabilizadas nem foi usado qualquer tipo de imobilização. Duas, quatro e seis semanas após a fratura, cinco ratos de cada grupo foram anestesiados e sacrificados por deslocamento cervical. O calo foi dissecado, preparado e analisado histologicamente. A análise histomorfológica foi realizada seis semanas após a fratura e o estágio de consolidação determinado a partir de escala de cinco pontos. RESULTADOS: Não houve diferenças histológicas e histomorfológicas entre os animais nos três diferentes estágios usados no experimento. Seis semanas após a fratura, os cinco animais de cada grupo apresentaram completa consolidação óssea. CONCLUSÃO: Nas condições estudadas, a suplementação de Vitamina C não acelerou o processo de consolidação de fraturas da tíbia de ratos. Nível de evidência II, estudo individual com delineamento experimental.

OBJECTIVE: To investigate the role of ascorbic acid supplementation on bone healing after rat tibia fracture. METHODS: Thirty male Wistar rats were randomly divided into Vitamin C (Group A) and sham (Group B) groups (15 rats each). Group A received 200 mg intraperitoneally per kg per day of ascorbic acid and Group B was given saline 5 ml per kg per day intraperitoneally once a day. The animals were caged in pairs and allowed free access to tap water and a standard rodent chow ad libitum. Fractures were produced manually, they were not stabilized, and unprotected weight-bearing was allowed. At two, four, and six weeks post-fracture, the rats in both groups were anesthetized and sacrificed by cervical dislocation. Callus tissue was dissected, prepared, and analyzed histologically. Histomorphological analysis was performed at six weeks post-fracture and the extent of fracture healing was determined using a five-point scale. RESULTS: There were no histological and histomorphological differences between drug-treated animals and the shamin the three different stages studied. By six weeks post-fracture, the five animals of each group had a complete bone union. CONCLUSION: Under the studied conditions, intraperitoneal Vitamin C supplementation does not accelerate the fracture healing process after experimental tibia fracture in rats. Level of evidence: Level 2, individual study with experimental design.

Alendronate-associated ulnar and tibial fractures: a case report.

Bisphosphonates are widely used to prevent osteoporotic fractures. Long-term use has resulted in unexpected subtrochanteric fractures in some elderly patients. We report a patient on long-term alendronate therapy who sustained fractures of the ulna and tibia sequentially over a 7-month period, without any trauma or fall.

A greenstick osteoporotic tibial fracture while on chemotherapy in a 12-year-old girl with osteosarcoma of the knee: does a preventive role exist for agents that reduce iatrogenic bone loss and skeletal-related events?

In patients with osteosarcoma several causative factors are implicated in the occurrence of osteoporosis, such as no weight-bearing, pre- and post-surgical immobilization, and neoadjuvant and adjuvant chemotherapy. Nevertheless, osteoporotic fractures are a rare complication in young patients. We report the case of a spontaneous greenstick fracture of the distal tibia occurring during adjuvant chemotherapy in a 12-year-old Caucasian girl. Among the various drugs, the main role of methotrexate was investigated. A review of the literature is also presented along with a discussion about the role of preventive agents able to reduce the occurrence of osteopenia and/or osteoporosis following cancer treatment.

Atypical insufficiency fracture of the tibia associated with long-term bisphosphonate therapy.

Osteoporosis is a major public health threat affecting millions of individuals in the United States. Bisphosphonate therapy is currently recognized as a first-line treatment of osteoporosis through the inhibition of osteoclast activity. Concerns have been raised about potential oversuppression of bone turnover and the development of atypical skeletal fragility associated with long-term use of bisphosphonates. A number of case reports in the literature have documented atypical insufficiency fractures in patients on long-term bisphosphonate therapy. This case outlines what we believe is the second documented atypical tibial insufficiency fracture in a patient on long-term bisphosphonate therapy, and highlights the need for increased awareness of atypical insufficiency fractures as well as the need for more data concerning the long-term effects of bisphosphonate therapy.

Severe bone defects and reduced mineralization caused by massive metallosis after total knee arthroplasty: histopathologic and bone morphometric findings.

We encountered a patient who developed metallosis after total knee arthroplasty (TKA), resulting in loosening of the implant, bone resorption, reduced bone formation, and fracture. The implant was replaced with a NexGen modular revision TKA system after autologous bone and hydroxyapatite granule grafting. Histopathologic examination showed accumulation of metallic debris and tartrate-resistant acid phosphatase-positive cells around the trabecular and cortical bone. Examination of hard tissue specimens showed a reduced bone volume (determined by bone histomorphometry) and an increase of all osteoid parameters, indicating disturbance of mineralization in addition to increased bone resorption.

Consolidaçäo da fratura após o uso prolongado de corticóide: estudo experimental em ratos / Fracture healing after prolonged use of steroids: experimental study in rats

O presente estudo tem por objetivo avaliar o efeito do uso prolongado de corticóide na consolidaçäo da fratura de tíbia em ratos. No experimento foram utilizados 50 ratos jovens; em 25 animais administrou-se hidrocortisona 0,4mg/100g/dia por via subcutânea (grupo A) e nos outros 25, usados como grupo controle, empregou-se soro fisiológico (grupo B). Após 30 dias da administraçäo de corticóide e soro fisiológico, todos os animais foram submetidos a fratura da tíbia direita. Os animais foram sacrificados com três, sete, 14, 21 e 35 dias pós-fratura. As tíbias fraturadas foram submetidas à análise histológica e radiológica para avaliaçäo das alterações induzidas pela droga. O grupo submetido à corticoterapia desenvolveu hematoma fraturário reduzido, assim como menor formaçäo de tecido cartilaginoso e, posteriormente, atraso na sua substituiçäo por tecido ósseo, mantendo o calo ósseo desorganizado e com pouca formaçäo de osso imaturo, quando comparado com o grupo controle. Verificou-se que o corticóide altera o processo de formaçäo do calo ósseo, retardando a consolidaçäo da fratura, fato detectado durante o período de avaliaçäo limitado pela pesquisa

[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.

Valproate therapy: predisposition to bone fracture?

A 13-year-old girl on valproate therapy had 20 fractures over a 4-year period between the ages of 5 years and 9 years. Once valproate was withdrawn, no further fractures occurred over the ensuing 4 years. Three other children manifested at least two fractures while on valproate antiepileptic therapy. These reports suggest that valproate, along with other known causes of demineralization (e.g., lack of exercise, diet, and genetic factors), predisposes patients to fractures.

Lower extremity stress fractures during intermittent cyclical etidronate treatment for osteoporosis.

During intermittent cyclical etidronate treatment, a lower extremity pain syndrome associated with stress fractures was observed in three osteoporotic patients. This report describes the development of stress fractures during initial cycles of treatment, with recurrence of symptoms in two patients when etidronate therapy was resumed. Further studies are needed to confirm whether stress fractures are associated with cyclic etidronate treatment and if so, the incidence and pathophysiology need to be determined.