Clinical trials indicate that oral BP reduce the incidence of osteoporotic fractures up to 60%. Although the safety of BP appears similar to placebo, adverse reaction reports have suggested an association between BP use and ONJ. On this concern, no epidemiological study including ‘validated’ cases of ONJ has been still conducted. A case-control study was nested into a cohort of fractured osteoporotic patients. An Adjudication Committee selected codes plausibly related to “true” cases of ONJ according to two levels of contiguity: level I ‘possibly contiguous with ONJ’ (e.g.: 730.08 ‘multiple bone infections, site unspecified’), level II ‘probably contiguous with ONJ’ (e.g.: 526.4 ‘jaw inflammation’). The Incidence Densities (IDs) of overall cases of ONJ and solely for those of level-II contiguity were computed. Up to 20 controls were matched to each case according to gender, age (±3 years), month and year of the cohort entry. Odds Ratio (OR; 95% Confidence Intervals (CIs)) of being exposed to BPs among cases vs. controls were estimated through conditional logistic regression model. Multivariable analysis includes use of steroids, proton pump inhibitors and diabetes as confounders. Within a cohort of 73,389 individuals, the ID of ONJ was 0.06 and 0.04 per 10,000 person-years for level-I and level-II criteria, respectively. After the application of exclusion criteria (i.e. previous use of BP, positive history of osteoporotic fractures, Paget and oncologic disease) 104 cases of ONJ (43 level I, 61 level II)were captured among 65,220 eligible participants (mean age: 66.5 yrs; 72.1% females). Among overall cases of ONJ the odds of being exposed to BPs was not different from controls (adjusted OR=1.1; 95% CI: 0.6-1.1). When the analysis was restricted to level-II cases, adjusted OR was 2.8 (95% CI: 1.3-5.9) higher for current users (last prescription within 1 year before the case’s date) of BP than never users. Incidence Density of ONJ was coherent with literature (Mavrokokki et al., 2007) when it was computed for level-II codes. These findings seem to suggest an association between use of oral BP and ONJ. Further analyses on definitively validated cases are needed.
Assessing the risk of Osteonecrosis of the Jaw (ONJ) due to Bisphosphonates (BP) therapy in the secondary prevention of osteoporotic fractures,
VACCHERI, ALBERTO;PICCINNI, CARLO;MONTANARO, NICOLA;
2011
Abstract
Clinical trials indicate that oral BP reduce the incidence of osteoporotic fractures up to 60%. Although the safety of BP appears similar to placebo, adverse reaction reports have suggested an association between BP use and ONJ. On this concern, no epidemiological study including ‘validated’ cases of ONJ has been still conducted. A case-control study was nested into a cohort of fractured osteoporotic patients. An Adjudication Committee selected codes plausibly related to “true” cases of ONJ according to two levels of contiguity: level I ‘possibly contiguous with ONJ’ (e.g.: 730.08 ‘multiple bone infections, site unspecified’), level II ‘probably contiguous with ONJ’ (e.g.: 526.4 ‘jaw inflammation’). The Incidence Densities (IDs) of overall cases of ONJ and solely for those of level-II contiguity were computed. Up to 20 controls were matched to each case according to gender, age (±3 years), month and year of the cohort entry. Odds Ratio (OR; 95% Confidence Intervals (CIs)) of being exposed to BPs among cases vs. controls were estimated through conditional logistic regression model. Multivariable analysis includes use of steroids, proton pump inhibitors and diabetes as confounders. Within a cohort of 73,389 individuals, the ID of ONJ was 0.06 and 0.04 per 10,000 person-years for level-I and level-II criteria, respectively. After the application of exclusion criteria (i.e. previous use of BP, positive history of osteoporotic fractures, Paget and oncologic disease) 104 cases of ONJ (43 level I, 61 level II)were captured among 65,220 eligible participants (mean age: 66.5 yrs; 72.1% females). Among overall cases of ONJ the odds of being exposed to BPs was not different from controls (adjusted OR=1.1; 95% CI: 0.6-1.1). When the analysis was restricted to level-II cases, adjusted OR was 2.8 (95% CI: 1.3-5.9) higher for current users (last prescription within 1 year before the case’s date) of BP than never users. Incidence Density of ONJ was coherent with literature (Mavrokokki et al., 2007) when it was computed for level-II codes. These findings seem to suggest an association between use of oral BP and ONJ. Further analyses on definitively validated cases are needed.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
