Report of a jaw osteonecrosis possibly causedby denosumab.

PURPOSE: To report a case of osteonecrosis of the jaw (ONJ) occurring in an implant area possibly related to denosumab, a relatively new antiosteoporotic agent. MATERIALS AND METHODS: Two months following the extraction of both maxillary first molars, a bilateral maxillary sinus floor elevation was performed on a 64-year-old female patient under a biannual 60 mg denosumab antiosteoporotic treatment. Seven months later, two implants were inserted in a single-stage procedure in each of the grafted sinuses. After 3 months, the implants underwent prosthetic rehabilitation at one side, and a series of failures that led to an ONJ instalment at the other side. RESULTS: The ONJ persisted over 7 months and was only resolved by a surgical approach consisting of a piezoelectric osteotomy and platelet-rich fibrin with a tension-free wound closure. CONCLUSIONS: A cumulative effect of denosumab is likely to be associated with a jaw osteonecrosis, which in this case was manageable using a surgical approach with no need to interrupt the appropriate drug treatment course. Conflict of interest statement: The authors certify that they are not affiliated with, or involved in any organisation or entity with any financial or non-financial interest in the subject matter or materials discussed in this manuscript.

Metabolome and proteome changes with aging in Caenorhabditis elegans.

To expand the understanding of aging in the model organism Caenorhabditis elegans, global quantification of metabolite and protein levels in young and aged nematodes was performed using mass spectrometry. With age, there was a decreased abundance of proteins functioning in transcription termination, mRNA degradation, mRNA stability, protein synthesis, and proteasomal function. Furthermore, there was altered S-adenosyl methionine metabolism as well as a decreased abundance of the S-adenosyl methionine synthetase (SAMS-1) protein. Other aging-related changes included alterations in free fatty acid levels and composition, decreased levels of ribosomal proteins, decreased levels of NADP-dependent isocitrate dehydrogenase (IDH1), a shift in the cellular redox state, an increase in sorbitol content, alterations in free amino acid levels, and indications of altered muscle function and sarcoplasmic reticulum Ca(2+) homeostasis. There were also decreases in pyrimidine and purine metabolite levels, most markedly nitrogenous bases. Supplementing the culture medium with cytidine (a pyrimidine nucleoside) or hypoxanthine (a purine base) increased lifespan slightly, suggesting that aging-induced alterations in ribonucleotide metabolism affect lifespan. An age-related increase in body size, lipotoxicity from ectopic yolk lipoprotein accumulation, a decline in NAD(+) levels, and mitochondrial electron transport chain dysfunction may explain many of these changes. In addition, dietary restriction in aged worms resulting from sarcopenia of the pharyngeal pump likely decreases the abundance of SAMS-1, possibly leading to decreased phosphatidylcholine levels, larger lipid droplets, and ER and mitochondrial stress. The complementary use of proteomics and metabolomics yielded unique insights into the molecular processes altered with age in C. elegans.