Osteonecrosis of the Jaw After Bisphosphonates Treatment in Patients with Multiple Myeloma

Bone lytic lesion in Multiple myeloma are the most commonly presented symptoms which require treatment with bisphosphonates (BPs). BPs are providing supportive care, reducing the rate of skeletal morbidity but evidently not abolishing it, the criteria for stopping their administration have to be different from those used for classic antineoplastic drugs, and they should not be stopped when metastatic bone disease is progressing. Osteonecrosis of the jaw (ONJ) has been associated recently with the use of BPs. The aim of these study is to evaluate the incidence of ONJ in patients with MM treated with mixed biphosphonates. We analyzed total 296 myeloma patients (150 male and 146 female). Mostly effected age group with 58,1% is age more than 60 years up to 88 years, diagnosed in our institution in the period 2005-2015. We used intravenous or oral forms of biphosphonates such as pamidronate, ibandronate, clodronate and zolendronic acid. The patients were evaluated for ONJ. The incidence of ONJ in our group of patients treated with Bps was 4,6% from our group of 260 patients 87,8% received BPs therapy and patients which haven’t received BPs 12,2%. From this group, 95,4% (248) didn’t show ONJ, and 4,6% (12) showed ONJ. The period of this treatment with BPs is an important risk factor for development of ONJ, average duration of BPs therapy in patients which show adverse effects is 26.8±13.7 months, from the total number of 12 patients that developed ONJ adverse effects, we have 8 patients which received treatment with Zolendronic acid and the remaining 4 patients which were treated with other BPs combinations without Zolendronic acid. All patients treated for MM must continue with the therapy with Zolendronic acid and Pamidronate, each patient must be individually treated according to his response of the treatment (dose, frequency and duration of therapy)

Primer and probe sequences used in four Custom TaqMan® SNP Genotyping Assays for the detection of polymorphisms 146 (N/S), 146 (N/D), 211 (R/Q) and 222 (Q/K).

<p>Primer and probe sequences used in four Custom TaqMan® SNP Genotyping Assays for the detection of polymorphisms 146 (N/S), 146 (N/D), 211 (R/Q) and 222 (Q/K).</p

Allelic frequencies (%) at codons 146, 211 and 222 of the <i>PRNP</i> gene locus.

<p>Allelic frequencies (%) at codons 146, 211 and 222 of the <i>PRNP</i> gene locus.</p

Genetic (F_ST) distances and corresponding P-values between goat breeds reared in Greece and other countries.

<p>Genetic (F_ST) distances and corresponding P-values between goat breeds reared in Greece and other countries.</p

Genotypic frequencies (%) and corresponding number of animals (in parenthesis) at codons 146, 211 and 222 of the <i>PRNP</i> gene locus.

<p>Genotypic frequencies (%) and corresponding number of animals (in parenthesis) at codons 146, 211 and 222 of the <i>PRNP</i> gene locus.</p

Unrooted Neighbor-Joining tree based on F_ST genetic distances.

<p>Colors indicate two major geographical clusters: Blue cluster includes: E_GR, Eghoria (Greece); S_GR, Skopelos (Greece); I_S_IT, Ionica (Southern Italy); RM_S_IT, Red Mediterranean (Southern Italy); D_GR, Damascus (Greece); D_CY, Damascus (Cyprus); K_TR, Kilis (Turkey); O_USA, Oberhasli (United States of America); S_USA, Saanen (United States of America); DB_UK, Dairy breeds (United Kingdom); T_USA, Toggenburg (United States of America); A_FR, Alpine (France); M_S_IT, Maltese (Southern Italy); DDS_S_IT, Derivata Di Siria (Southern Italy); G_S_IT, Garganica (Southern Italy); GI_S_IT, Girgentana (Southern Italy). Red cluster includes: S_TR, Saanen (Turkey); V_N_IT, Valdostana (Northern Italy); A_USA, Alpine (United States of America); S_IT_N, Saanen (Northern Italy); A_TR, Akkeci (Turkey); S_JP, Saanen (Japan); CDA_N_IT, Camosciata Delle Alpi (Northern Italy); R_N_IT, Roccaverano (Northern Italy); P_S_IT, Pantellaria (Southern Italy); S_FR, Saanen (France); LM_USA, La Mancha (United States of America), D_TR, Damascus (Turkey); N_USA, Nubian (United States of America); B_CN, Boer (China).</p

Genetic (F_ST) distances (above diagonal) and corresponding P-values (below diagonal) among Eghoria, Skopelos and Damascus breeds.

<p>Genetic (F_ST) distances (above diagonal) and corresponding P-values (below diagonal) among Eghoria, Skopelos and Damascus breeds.</p

WB_DP_map

map file associated with the ped fil

WB_DP_ped

ped file with WB and DP individual

MOESM11 of Genome-wide SNP data unveils the globalization of domesticated pigs

Additional file 11: Figure S9. Distribution of haplotype diversity for pig populations across the world. Diamonds and vertical bars represent means and standard deviations of number of haplotypes respectively in 5-SNP s (A), 10-SNP (B), and 15-SNP (C) windows across the genome for each population with a minimum of 10 individuals