TASK DEFINITION: In this task, you are given a passage which has a question and the context. You have to generate an answer to the question based on the information present in the context.
PROBLEM: Context: Strontium ranelate reduces fracture risk in postmenopausal women with osteoporosis. Evidence from non-clinical studies and analyses of bone markers in phase III trials indicate that this is due to an increase in osteoblast formation and a decrease of osteoclastic resorption. The aim of this work was to investigate, in human cells, the mechanisms by which strontium ranelate is able to influence the activities of osteoblasts and osteoclasts.', 'Human primary osteoblasts were used to examine effects of strontium ranelate on replication (thymidine incorporation), differentiation (Runx2 and alkaline phosphatase) and cell survival (cell counts and caspase activity). Osteoprotegerin (OPG) was measured by quantitative reverse transcription PCR (qRT-PCR) and elisa and receptor activator of NFkappaB ligand (RANKL) by qRT-PCR and Western blot. As strontium ranelate has been proposed as an agonist of the calcium-sensing receptor (CaSR), the involvement of CaSR in the effects of strontium ranelate on OPG and RANKL expression, and cell replication was examined using siRNA.', 'Strontium ranelate increased mRNA and protein levels of OPG and suppressed those of RANKL. Strontium ranelate also stimulated osteoblast replication and differentiation and increased cell survival under stress. Knocking down CaSR suppressed strontium ranelate-induced stimulation of OPG mRNA, reduction of RANKL mRNA, and increase in replication, indicating the involvement of CaSR in these responses.\Question: Do osteoblasts play key roles in the mechanisms of action of strontium ranelate?

SOLUTION: Our results demonstrate that osteoblasts play a key role in the mechanism of action of the anti-fracture agent, strontium ranelate by mediating both its anabolic and anti-resorptive actions, at least in part, via activation of CaSR.

PROBLEM: Context: Hepatic osteodystrophy has been reported in patients with various chronic liver diseases, including liver cirrhosis. However, it has not been well investigated in patients with hepatitis B virus infection. The aim of this study was to investigate the association between hepatitis B surface antigen (HBsAg) seropositivity and bone mineral density (BMD) in a population representative of normal Koreans.', 'Subjects with both HBsAg and BMD levels examined during the 2008-2010 Korea National Health and Nutrition Examination Surveys were included. HBsAg-seropositive (+) subjects were compared with those who were HBsAg-seronegative (-). BMD was measured at the lumbar spine and femur by dual-energy X-ray absorptiometry. Multivariable logistic regression was performed for BMD .', 'In total, 11,306 participants were included in this study, among which 423 (3.7\xa0%) were HBsAg(+): 153 premenopausal female (3.4\xa0%), 83 postmenopausal female (3.5\xa0%), and 187 male (4.2\xa0%). Multivariable logistic regression analysis adjusted for age and body mass index showed that HBsAg(+) male had significantly lower BMD of the femoral neck than HBsAg(-) male (0.810\xa0±\xa00.009 vs. 0.827\xa0±\xa00.002\xa0g/cm(2), p\xa0=\xa00.035). Further adjustment for waist circumference, smoking, drinking, exercise, income, occupation, and vitamin D levels showed that HBsAg(+) male had significantly lower BMD of the femur neck (0.810\xa0±\xa00.010 vs. 0.831\xa0±\xa00.002\xa0g/cm(2), p\xa0=\xa00.032) and lumbar spine (0.953\xa0±\xa00.011 vs. 0.974\xa0±\xa00.003\xa0g/cm(2), p\xa0=\xa00.049) than HBsAg(-) male.\Question: Are males seropositive for hepatitis B surface antigen at risk of lower bone mineral density : the 2008-2010 Korea National Health and Nutrition Examination Surveys?

SOLUTION: HBsAg seropositivity was significantly associated with lower BMD in male. Future long-term prospective studies investigating bone turnover markers and hormones are needed to better understand the pathophysiology and clinical significance of chronic hepatitis B virus-related hepatic osteodystrophy.

PROBLEM: Context: In the presented study the effect of age and cytogenetics on clinical outcome in acute myeloid leukemia (AML) was evaluated. The 1225 patients with de novo AML were separated according to age as follows: A1: 16 to 49 years (n=442), A2: 50 to 59 years (n=246), A3: 60-69 years (n=333), A4: 70 years and older (n=204).', 'Patients were categorized with respect to cytogenetics into 5 groups: C1: t(15;17) (n=107), C2: CBF-AML/inv(16)/t(8;21) (n=171), C3: 11q23/MLL (n=42), C4: complex aberrant karyotype (n=130), C5: other: normal, other abnormalities, 5q-/-5, 7q-/-7, inv(3)/t(3;3), other 3q abnormalities (n=746). For each age category univariate cox regression analysis was performed using age as a continuous variable and C1 to C5 as dichotomous variables.', 'In cohort A1 all parameters were significantly associated with overall survival (OS). However, in multivariate analysis all cytogenetic parameters were independently correlated with OS, while age was not. In cohort A2 only CBF and complex aberrant karyotype were significantly correlated with OS. In A3 t(15;17), complex karyotype and age, and in A4 only complex karyotype and age were significantly associated with OS in univariate and multivariate analyses. Within all cytogenetic subgroups except AML 11q23/MLL there were significant associations between age and OS.\Question: Does the influence of age on prognosis of de novo acute myeloid leukemia differ according to cytogenetic subgroups?

SOLUTION:
(i) Both age and cytogenetics are independent prognostic parameters in AML;(ii) up to the age of 49 years age has no major impact on prognosis while the karyotype has; (iii) in patients 50 years and older the influence of age on outcome increases, and (iv) cytogenetics show an independent effect on survival also in patients over 60 years old.