Bruck syndrome: A rare case presentation with isolated lower extremity contractures and multiple postoperative peri-implant fractures

Bruck syndrome, characterized by congenital brittle bones and multiple joint contractures, is a rare variant of osteogenesis imperfecta. Here, we report the case of a 7-year-old male patient who presented with a fractured shaft of the femur following trivial trauma. He was diagnosed case of arthrogryposis multiplex congenital with deformities involving both knees and ankle. He had a history of bilateral femoral fractures during birth. Due to the knee contracture and a narrow canal, we fixed the fracture by plating. However, the patient developed peri-implant fractures proximal to the plate. Due to the presence of multiple peri-implant fractures and joint contractures, we diagnosed the patient with Bruck’s syndrome and initiated intravenous bisphosphonate therapy. Subsequently, the patient developed one more fracture in the contralateral femur. This case signifies the importance of screening all patients with multiple congenital contractures and recurrent fractures for Bruck syndrome.

An unusual case of bone regeneration of a necrotic mandible with pathologic fracture in an elderly hemodialysis patient with medication-related osteonecrosis of the jaw: a case report and review of the literature

Background Bisphosphonates are frequently used for osteoporosis. Medication-related osteonecrosis of the jaw, a complication of bone-modifying agents, including bisphosphonates or angiogenic inhibitors, can be challenging to treat in elderly patients with numerous preexisting conditions. Achieving good treatment outcomes is especially difficult in patients with pathological fractures accompanied with extraoral fistulae. Case presentation We report an unusual case of prominent bone regeneration following palliative surgical treatment in a 72-year-old Japanese female patient undergoing hemodialysis. She previously had severe osteoporosis due to renal osteodystrophy and was receiving antiresorptive intravenous bisphosphonate. Computed tomography revealed a discontinuous left lower mandibular margin with a pathologic fracture and extensive, morphologically irregular sequestrum formation (80 × 35 × 20 mm). The patient was diagnosed with stage III medication-related osteonecrosis of the jaw and pathologic mandibular fracture. Immediately before the surgery, the anticoagulant used for dialysis was changed from heparin to nafamostat mesylate to reduce the risk of intraoperative bleeding. Sequestrectomy was performed under general anesthesia. Postoperative infection was not observed, the intraoral and submandibular fistula disappeared, and, surprisingly, prominent spontaneous bone regeneration was observed postoperatively at 6 months. Despite the severe systemic condition of the patient, the conservative surgical approach with sequestrectomy has yielded desirable results for more than 6 years since the surgery. Conclusions This rare report of spontaneous bone regeneration in a patient of advanced age and poor general condition is the oldest case of mandibular regeneration ever reported.

Characteristics of patients with osteonecrosis of the jaw with oral versus intravenous bisphosphonate treatment

Purpose This retrospective study was aimed to evaluate the clinical characteristics and treatment outcomes in patients with osteonecrosis of the jaw who were receiving oral versus intravenous (IV) bisphosphonate (BP). Materials and methods This retrospective study enrolled subjects who had been diagnosed with medication-related osteonecrosis of the jaw (MRONJ) during the period from July 2010 to June 2014. Information regarding the following demographic and clinical characteristics was collected: demographic data, administration route and type of BP, duration of BP medication, primary disease, number of involved sites, location of the lesion, number of surgeries, outcome of treatments, and laboratory test. All the patients were divided into oral and IV BP groups; and the between-group differences were compared. Results Total 278 patients were divided into two groups as per the route of BP administration. The proportion of oral BP-related MRONJ group were more dominant over IV BP group (oral BP, n = 251; IV BP, n = 27). In the IV BP group, the average dosing duration (31.4 months) was significantly shorter than that in the oral BP group (53.1 months) (P < 0.001). The average number of involved sites in the oral BP group (1.21 ± 0.48) was smaller than that in the IV BP group (1.63 ± 0.84) (P < 0.001). The average number of surgeries was higher in the IV BP group (1.65 ± 0.95) as compared to that in the oral BP group (0.98 ± 0.73) (P < 0.001). Outcome after the surgery for MRONJ after IV BP was poor than oral BP group. Conclusion IV administration of BP causes greater inhibition of bone remodeling and could lead more severe inflammation. Therefore, even if the duration of IV administration of BP is shorter than that of oral BP, the extent of the lesion could be more extensive. Therefore, the result suggests that the MRONJ after IV BP for cancer patients needs to be considered as different characteristics to oral BP group for osteoporosis patents.

Comparison of the Effect of Oral Versus Intravenous Bisphosphonate Administration on Osteoclastogenesis in Advanced-Stage Medication-Related Osteonecrosis of the Jaw Patients

It is yet unknown whether the intravenous administration route alone can fully account for the exacerbation of medication-related osteonecrosis of the jaw (MRONJ). The purpose of this retrospective study was to identify the potential role of the bisphosphonate (BP) administration route as an independent prognostic factor for non-cancerous, stage III MRONJ patients. Bone samples were retrospectively obtained from two groups of osteoporosis patients who underwent surgery for the treatment of stage III MRONJ. Among the subjects, 10 had a history of only oral BP consumption and 10 of intravenous (IV) BP administration. The samples were assessed for osteoclast morphology and immunohistochemical expression of the receptor activator of NF-κB ligand (RANKL), osteoprotegerin (OPG), and potassium calcium-activated channel subfamily N member 4 (Kcnn4). Although the osteoclasts derived from both groups exhibited no significant differences in the mean quantity, diameter, and nuclearity, significantly attenuated tartrate-resistant acid phosphatase activity was noted among the IV BP-induced MRONJ bones compared to those of the oral BP group. Significant suppression of the RANKL/OPG ratio and Kcnn4 expression among the retrieved bones of IV BP group patients was also noted. Our results indicate the potential of the BP administration route as an independent prognostic factor for advanced-stage MRONJ, regardless of the dosage or indication for which the BP was prescribed.

Retrospective Evaluation of Acute Kidney Injury After Zoledronic Acid Administration to Dogs With Malignant Osteolysis

Zoledronic acid (ZOL) is an intravenous bisphosphonate indicated for the use of hypercalcemia of malignancy and management of bony metastases. Its therapeutic effect lies in the targeting of malignant osteoclasts; however, administration can be associated with renal toxicity. The objective of this retrospective study was to evaluate the frequency and severity of acute kidney injury (AKI) following ZOL administration in a cohort of cancer-bearing dogs. A pharmacy search was conducted to identify dogs that received a dose of ZOL between June 2016 and July 2019. Inclusion criteria included baseline and post-treatment chemistry panels. Medical records were reviewed to obtain clinical data including signalment, dose, dosage, number of treatments administered, and changes in renal function. Forty-four dogs met the inclusion criteria. Median number of doses administered was three [interquartile range (IQR), 2–5]. The median highest creatinine value occurred after a median of one dose (IQR, 1–2 doses) compared with the median highest value of blood urea nitrogen, phosphorus, and potassium, which occurred after a median of two doses (IQR, 1–3). Six (13.6%) dogs developed an AKI, and one dog (2.3%) had progression of an existing azotemia after treatment with ZOL was initiated. Two dogs (4.5%) had ZOL treatment discontinued secondary to development of azotemia. Use of concurrent administration of non-steroidal anti-inflammatory drugs or anesthesia did not significantly increase the risk of AKI in this cohort of dogs. Acute kidney injury is observed infrequently in cancer-bearing dogs treated with ZOL and is generally mild to moderate in severity; discontinuation of ZOL due to AKI is uncommon.

Severe hypercalcaemia secondary to relapsed Graves’ disease

A 21-year-old woman presented to hospital with abdominal pain and nausea. She had a history of Graves’ disease which had been effectively treated with carbimazole for 15 months. Investigations revealed a serum adjusted calcium level of 3.69 mmol/L with a suppressed parathyroid hormone, thyroid stimulating hormone <0.01 mu/L (0.2–5.0) and free T4 of 76.1 pmol/L (9-24). She was treated as a relapsed case of Graves’ disease and started on propylthiouracil. Calcium levels continued to increase over the next 3 days despite adequate fluid resuscitation. A decision was taken to administer intravenous bisphosphonate (pamidronate) which resulted in a lowering of calcium levels. She became mildly hypocalcaemic following treatment with pamidronate which was presumed secondary to low vitamin D and oral vitamin D replacement was commenced. This case was unique as this is to our knowledge the most significant hypercalcaemia observed in a patient with hyperthyroidism. All other causes of hypercalcaemia were excluded. The learning points were recognising hypercalcaemia as a complication of thyrotoxicosis and the risk of hypocalcaemia following bisphosphonate therapy with low vitamin D stores.

The effect of pamidronate delivery in bisphosphonate-naïve patients on neutrophil chemotaxis and oxidative burst

The pathogenesis of medication-related osteonecrosis of the jaw (MRONJ), a morbid condition associated with bisphosphonate administration, has not been fully elucidated. Recent research utilizing a murine model has revealed that the neutrophil becomes dysfunctional following exposure to bisphosphonates. Accordingly, the impairment of neutrophil function could play an important role in the pathogenesis of MRONJ via an infectious mechanism mediated by the suppression of the innate immune system. Currently, the existing human data are insufficient to substantiate this theory. To investigate, we isolated neutrophils from blood and oral rinse samples from bisphosphonate-naïve patients who were recently diagnosed with multiple myeloma both prior to and one month following their initial infusion of pamidronate, an intravenous bisphosphonate agent. Stimulated blood and oral neutrophil superoxide production and chemotactic capabilities were found to be impaired relative to baseline values. These results suggest that impaired neutrophil function may partially contribute to the aetiology underlying the pathophysiological processes linked to the development of MRONJ. Further, as the functional status of circulating neutrophils was reflected in the oral cavity where sampling can be accomplished in a non-invasive fashion, it is conceivable that neutrophil function could serve as a potential biomarker for MRONJ prognostication.