Severe and Symptomatic Calcium Disorders Caused by Secondary Bone Disease in a Patient with a Thyroid Storm

A patient with Graves’ disease was admitted with a thyroid storm. She had severe hypercalcaemia caused by thyrotoxicosis. Treatment was complicated by vomiting and diarrhoea. With intravenous ondansetron, hydration and bisphosphonates, GI symptoms improved and oral thyreostatics could be started. This, combined with bisphosphonate administration, resulted in a mild hungry bone syndrome.

Unwrapping microcomputed tomographic images for measuring cortical osteolytic lesions in the 5T2 murine model of myeloma treated by bisphosphonate

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Bifosfonatos e implantes dentales, ¿son incompatibles?: revisión de la literatura

Introducción: La osteonecrosis de los maxilares ha sido descrita en pacientes que toman bifosfonatos y han sido sometidos a cirugía dentoalveolar. Actualmente, la terapia con bifosfonatos e implantes dentales es un tratamiento muy común en adultos. Objetivos: Evaluar, a través de una revisión de la literatura, si la osteointegración del implante dental podría disminuir en pacientes que toman bifosfonatos orales o intravenosos. Además, se analiza el riesgo que tienen estos pacientes de desarrollar osteonecrosis de los maxilares. Material y métodos: Se realizó una búsqueda a través de la base de datos Medline (PubMed) de los artículos publicados en inglés en los últimos 15 años que incluyeran las palabras clave "bisphosphonates and dental implants", "bisphosphonates and orthopaedic implants" y "osteonecrosis of the jaws and dental implants". Conclusiones: El tratamiento con bifosfonatos no disminuye la osteointegración del implante dental, aunque estos resultados se han obtenido en base a estudios retrospectivos en humanos. Se han descrito casos de osteonecrosis de los maxilares relacionada con bifosfonatos en estos pacientes, sobre todo tras tratamiento prolongado.

Exploring the role of the α-carboxyphosphonate moiety in the HIV-RT activity of α-carboxy nucleoside phosphonates

As α-carboxy nucleoside phosphonates (α-CNPs) have demonstrated a novel mode of action of HIV-1 reverse transcriptase inhibition, structurally related derivatives were synthesized, namely the malonate 2, the unsaturated and saturated bisphosphonates 3 and 4, respectively and the amide 5. These compounds were evaluated for inhibition of HIV-1 reverse transcriptase in cell-free assays. The importance of the α-carboxy phosphonoacetic acid moiety for achieving reverse transcriptase inhibition, without the need for prior phosphorylation, was confirmed. The malonate derivative 2 was less active by two orders of magnitude than the original α-CNPs, while displaying the same pattern of kinetic behavior; interestingly the activity resides in the “L”-enantiomer of 2, as seen with the earlier series of α-CNPs. A crystal structure with an RT/DNA complex at 2.95 Å resolution revealed the binding of the “L”-enantiomer of 2, at the polymerase active site with a weaker metal ion chelation environment compared to 1a (T-α-CNP) which may explain the lower inhibitory activity of 2.

Osteonecrose dos maxilares associada a fármacos anti-reabsorção óssea

Os fármacos anti-reabsorção óssea mais utilizados atualmente são os bifosfonatos que são medicamentos que inibem a actividade osteoclástica. O mecanismo de ação destes fármacos consiste na redução da reabsorção óssea pois inibem a apoptose dos osteoclastos e promovem a inibição da angiogénese. Estes fármacos são utilizados no tratamento de doenças como a osteoporose, hipercalcemia, doença de Paget e em pacientes oncológicos com metástases ósseas de tumores sólidos e mieloma múltiplo. Por outro lado, estes fármacos além de todos os benefícios que têm para os pacientes nestas condições, podem ter como complicação a osteonecrose dos maxilares (ONM). A ONM é uma complicação oral grave caracterizada, na maioria, por uma osteomielite inicial que normalmente evolui para uma exposição de osso necrosado acompanhada por dor na maxila ou na mandíbula. Nos doentes oncológicos têm sido diagnosticados vários casos de necrose óssea mais frequentemente na mandíbula. Esta patologia (ONM) apesar de ter baixa incidência e do seu aparecimento ser relativamente recente, levou à introdução de algumas recomendações internacionais para o uso de bifosfonatos, principalmente em pacientes oncológicos. Para a execução deste trabalho recorri a fontes de pesquisas como as bases de dados como a PubMed, B-On e, também ao Repositório Institucional da Universidade Fernando Pessoa das quais resultaram 198 artigos e duas monografias realizadas por exalunos da Universidade Fernando Pessoa. Com a realização deste trabalho foi possível esclarecer algumas dúvidas acerca dos efeitos que os fármacos anti-reabsorção óssea têm no organismo e mais especificamente na cavidade oral, de forma a estar consciente dos riscos que estes pacientes correm, caso lhes sejam realizados procedimentos como é o caso, das exodontias ou da colocação de implantes.

An examination of verbal descriptors of cancer-induced bone pain and neuropathic cancer pain

Aims: The aim of the thesis was to identify verbal descriptors of cancer induced bone pain (CIBP) and neuropathic cancer pain (NCP). An examination of the verbal descriptors associated with these two pain syndromes further considered the relationship between common verbal descriptors, cancer type, performance status and analgesia. Methods: The project was conducted in two phases; Phase one was a systematic review of the literature to examine current evidence of verbal descriptors in CIBP and NCP. Phase two utilised secondary data analysis methodology. Data from 120 patients with confirmed CIBP and 61 patients with confirmed NCP were deemed eligible for entry into a de novo database for secondary analysis. Key descriptive data were considered such as gender, ECOG and pain scores to characterise the patient population. Verbal descriptors of CIBP and NCP were considered in detail across the secondary de novo database. Results: Gender was not identified as a diagnostic characteristic of CIBP and NCP with similar distribution across prevalence of pain reporting and also pain severity. Patients with breast (n=52,43.3%), prostate (n=35,29.2%) and lung (n=14,11.7%) cancer were found to be at an increased risk of CIBP. Those with NCP more was found more commonly among patients with breast cancer (n=21,34.4%). Patients with CIBP were found to have an ECOG performance of 1 (n=49, 40.8%) or 2 (n=43, 35.8%) which was lower than those with NCP with an ECOG of 0 (n=32, 52.5%) or 2 (n=18, 29.5%). Comparisons were made across analgesia and treatment options for CIBP and NCP. Patients with CIBP received a greater variety of treatment options including bisphosphonates and radiotherapy while patients with NCP were more commonly treated with analgesia alone. Patients with CIBP and NCP were taking strong opioids, however those with NCP (n=45, 73.8%) were more likely to utilise strong opioids than those with CIBP (n=61, 50.8%). It was noted that those with NCP required a daily morphine equivalence of almost 50% higher than those with CIBP. Average consumption of opioids was 155.6mg, for patients with NCP, compared to 76mg in patients with CIBP. Common verbal descriptors of CIBP and NCP were identified. The most common verbal descriptors for CIBP were aching, gnawing and throbbing and the most common verbal descriptors of NCP were aching, tender and sharp. Of the most common 6 descriptors for CIBP and NCP only one descriptor was unique to each pain type, gnawing for CIBP and stabbing for NCP. Conclusions: Patients with CIBP and NCP use similar verbal descriptors to characterise their pain with gnawing being unique to CIBP and stabbing being unique to NCP in the data considered within project. Further research is required to explore verbal descriptors which are both common and unique to CIBP and NCP. Further exploration of verbal descriptors would assist development of a comprehensive pain assessment tool which would enhance pain assessment for nurses, clinicians and patients.