P066 Orthopedic complications of osteogenesis imperfecta

Background Osteogenesis imperfecta (OI) is an inherited connective tissue disorder including various skeletal manifestations. Bone fragility, vertebral body malformation and length lower limbs inequality are often responsible for orthopedic complications. The aim of our study was to determine orthopedic complications of OI and to specify management modalities in rheumatology. Methods We conduct a retrospective study based on the files of children referred to the rheumatology departement over the last 15 years, for treatment of OI. The evaluation was clinical and radiological. Clinical examination included joint and spine assessment. An X-ray of the spine and painful joints associated with a quantitative densitometry were requested. Results Five patients were collected, their mean age was 9 years. All patients had peripheral fracture. Joint assessment revealed a flessum of the elbow and a reduction of the motion of hip in 40% of cases. Scoliosis was noted also in 40% of cases. The average of spine Z –score was -3, 4. All children had benefited from oral calcium and vitamin D supplementation associated with cyclic intravenous bisphosphonates and an adapted rehabilitation protocol. Surgical management was often needed in 2 cases. Discussion and Conclusion Orthopedic complications during OI are essentially the consequence of lower bone mineral density which would cause peripheral or vertebral fracture. Indeed, some other factors like length inequality, pelvic obliquity, ligamentous laxity and inter-vertebral disc abnormalities could be involved in scoliotic progression. The management of these skeletal complications must be early and multidisciplinary in order to improve the prognosis and the quality of life of the patient

Osteogenesis imperfecta: minimizing complications in oral surgery/orthodontic treatment

Osteogenesis imperfecta (OI) is a rare genetic condition that affects connective tissue and is primarily characterized by bone fragility. Owing to the progressive nature of the disease, patients require life-long management of the adverse effects and the subsequent complications they can experience. Since the introduction of bisphosphonates as a treatment modality, complications and bone deformities associated with OI have been minimized. However, intravenous bisphosphonates in young patients could present a new era of difficulties for the dental profession. We report on a case of a patient with OI who presented with severe orthodontic crowding and describe the multidisciplinary treatment planning required to minimize potential complications. CPD/Clinical Relevance: General dental practitioners should be aware of the characteristics of osteogenesis imperfecta and the potential complications associated with dental treatment.

Medication-Related Osteonecrosis of the Jaws and CDK4/6 Inhibitors: A Recent Association

The purpose of the present study was to estimate the prevalence of cyclin-dependent kinase (CDK) 4/6 inhibitors use among cancer patients from the medication-related osteonecrosis of the jaw (MRONJ) cohort of the University of Messina. We retrospectively reviewed the records of all patients with either intravenous bisphosphonates or denosumab-related MRONJ reported in the electronic health records of the Unit of Oral Surgery, School of Dentistry, University of Messina between the first quarter of 2018 and the first quarter 2020 to identify eligible patients. We observed six cases of MRONJ associated with CDK4/6 inhibitors concomitantly with intravenous bisphosphonates and/or denosumab in breast cancer patients. The CDK4/6 inhibitors registered were palbociclib (n = 5) and abemaciclib (n = 1). Data of cancer patients diagnosed with MRONJ in the same period (n = 10) were extracted for comparison. The comparative assessment with this group of patients showed a similar distribution of MRONJ stage ranged and clinical course after treatment. The degree of risk for osteonecrosis in patients taking these new classes of drugs is uncertain but warrants awareness and close monitoring. The role of premedication dental evaluation as a prevention strategy has been acknowledged for cancer patients about to initiate intravenous bisphosphonates and/or denosumab for treatment of bone metastasis, but additional attention should be paid to whom are assuming CDK4/6 inhibitors because of their oral adverse events.

Safety of Intravenous Bisphosphonates for the Treatment of Hypercalcemia in Patients With Preexisting Renal Dysfunction

Background Although intravenous (IV) bisphosphonates are first-line medications for the management of hypercalcemia, studies examining their use in patients with preexisting renal dysfunction are limited. Objective The objective of this study is to describe the safety and efficacy of pamidronate and zoledronic acid in the treatment of hypercalcemia in patients with baseline renal dysfunction. Methods A retrospective analysis was conducted of IV pamidronate and zoledronic acid in adult patients with hypercalcemia and creatinine clearance (CrCl) <60 mL/min. The primary endpoint was incidence of all-grade serum creatinine (SCr) elevations. Secondary endpoints included refractory hypercalcemia, hypocalcemia, osteonecrosis of the jaw (ONJ), corrected serum calcium (CSC) decrease ≥1.0 mg/dL by day 7 of bisphosphonate administration, and normalization of CSC ≤10.5 mg/dL by days 10 and 30. Results A total of 113 patients were included (n = 55 pamidronate, n = 58 zoledronic acid). The primary endpoint of all-grade SCr elevation occurred in 28 (24.8%) patients. Grades 3/4 SCr elevations occurred in 10.9% of patients treated with pamidronate and 1.7% of patients receiving zoledronic acid. Approximately 16% and 14% of patients developed grades 1 and 2 hypocalcemia, respectively, and there were no cases of ONJ. Overall, 64.6% of patients achieved normalization of CSC by day 10, and there were no statistical differences between bisphosphonate type and renal function. Conclusions and Relevance The analysis suggests an association between IV bisphosphonates and increased rates of SCr elevations among patients with preexisting renal dysfunction. Future prospective studies are necessary to elucidate these findings.

Cinacalcet for the Treatment of Humoral Hypercalcemia of Malignancy: An Introductory Case Report with a Pathophysiologic and Therapeutic Review

Hypercalcemia is an ominous development in the course of malignancy associated with a mean survival of only several months. A majority of cases of hypercalcemia are related to humoral hypercalcemia of malignancy (HHM), where hypercalcemia is caused by increased levels of circulating parathyroid hormone-related protein (PTHrP). Mainstay treatments in the management of HHM are intravenous fluids, intravenous bisphosphonates, and subcutaneous denosumab, although hypercalcemia oftentimes recurs despite these efforts. We present a case of advanced non-small cell lung cancer with PTHrP-mediated hypercalcemia that proved resistant to standard therapy. A trial of oral cinacalcet was initiated and improved calcium levels for 2 months despite a progressive rise in PTHrP and prior to subsequent disease progression. Based on the current body of literature, we propose that this calcium-lowering effect of cinacalcet occurs due to a potential effect on renal calcium excretion.

Care and management of bisphosphonate-associated osteonecrosis of jaw in patient with pathological fracture of mandible: case study

This is a case study of patient with bisphosphonate associated osteonecrosis of the mandible after an extraction of teeth 4.6 and 4.7 complicated with pathological fracture while receiving intravenous bisphosphonates is discussed. The patients presenting signs and symptoms are reviewed. Bisphosphonates induced osteonecrosis definition and are reviewed management.

Treatment of bone metastases by intravenous bisphosphonates and denosumab in breast cancer

Les métastases osseuses sont fréquentes dans le cancer du sein. Elles sont à l’origine d’une morbidité importante, entrainant des fractures, des douleurs osseuses, une compression médullaire ou une hypercalcémie. Les bisphosphonates intraveineux et le denosumab, associés aux différents traitements multidisciplinaires, améliorent la qualité de vie des patients. En effet, ils permettent une réduction des complications osseuses et la survenue des événements osseux.