Diminishing value from multiple serial bone densitometry in women receiving anti-resorptive medication for osteoporosis

Background The value of serial bone mineral density (BMD) monitoring while on osteoporosis therapy is controversial. Objective We determined the percentage of women classified as suboptimal-responders to therapy with anti-resorptive medications according to two definitions of serial BMD change. Design Cohort study using administrative databases. Setting Single-payer government health system in Manitoba, Canada. Patients Post-menopausal women aged 40 years or older receiving anti-resorptive medications and having 3 sequential BMD measures. Women stopping or switching therapies were excluded. Methods The percentage of women whose spine or hip BMD decreased significantly during the first or second interval of monitoring by BMD was determined. Suboptimal-responder status was defined as BMD decrease during both monitoring intervals or BMD decreased from baseline to final BMD. Results There were 1369 women in the analytic cohort. Mean BMD monitoring intervals were 3.0(0.8) and 3.2(0.8) years respectively. In the first interval, 3.2% and 6.5% of women had a decrease in spine or hip BMD; 8.0% and 16.9% had decreases in the second monitoring interval, but only 1.4% showed repeated losses in both intervals. Considering the entire treatment interval, only 3.2% and 7.4% showed BMD loss at spine or hip. Limitations Results may not apply to situations of poor adherence to anti-resorptive medication or anabolic therapy use. Interpretation Among women highly adherent to anti-resorptive therapy for osteoporosis, a very small percentage sustained BMD losses on repeated measures. The value of multiple serial BMD monitoring to detect persistent suboptimal-responders should be questioned.

Different response to imatinib and nilotinib in relationship with the time of administration

Here we describe a case of a young patient with chronic myeloid leukemia at low risk, according to the Sokal index. After cytoreduction with hydroxyurea, the patient started imatinib at standard dose (400 mg/day) obtaining a minor cytogenetic response (Ph+ 42.5%) after six months of treatment.Considering the low imatinib concentration evaluated with the blood level testing, we increased the dose of imatinib at 600 mg/day. After about 3 months treatment the patient presented a partial cytogenetic response (Ph+ 30%). Therefore he was considered suboptimal responder according to European LeukemiaNet (ELN) recommendations 2006. For this reason he switched to second generation tyrosine kinase inhibitor nilotinib, at dose 800 mg/die. After switching to nilotinib the patient reached complete cytogenic response and major molecular response, maintained until last molecular evaluation.This kind of patient shows a different response for imatinib and nilotinib, whereas nilotinib therapy has shown to be safe and efficacy.

The Clinical Utility of the 1-Deamino-8-D-Arginine Vasopressin (DDAVP) Trial in the Management of Patients with Von Willebrand Disease: A Retrospective Study.

DDAVP has been shown to be effective in securing hemostasis in certain patients with mild and moderate von Willebrand disease (vWD) undergoing hemostatic challenge. However as the response to this agent is heterogeneous, it is currently recommended that patients with vWD undergo a therapeutic trial of this agent prior to any elective invasive procedures. We performed a retrospective review of DDAVP response in patients with vWD in order to determine which patient groups most benefit from a DDAVP trial, and the optimum testing protocol, particularly examining the need to recall the patient for testing at 24 hours. Between 1990–2006 we identified 129 patients undergoing DDAVP trial for a historical diagnosis of vWD based on a previous low von Willebrand factor antigen (vWF:Ag), ristocetin cofactor activity (vWF:RiCoF) or collagen-binding activity (vWF:CBA), and a bleeding history. Twenty-one patients were excluded from analysis having normal vWD parameters prior to DDAVP infusion. The median age of patients was 25 years, (range 4–64), with 60% being female. The distribution of vWD subtypes was as follows: 94 type 1, eight type 2A, and six with a bleeding phenotype and no abnormality other than mildly reduced vWF:RiCoF. DDAVP was administered by IV infusion with samples taken for testing pre-infusion and between 1–2 hours post infusion. Additional testing at 24 hours was performed in the majority after 2003. A complete response (CR) was defined as an increase in all vWD parameters to within the normal range (vWF:Ag [50–200%], vWF:RiCoF [50–150%], vWF:CBA [50–200%]); a partial response (PR), an increase to between 30% and lower limit of normal. Results: In the type 1 vWD cohort, at one hour post infusion 75/94 experienced CR, 15/94 PR and 4/94 no response (NR). All patients with baseline vWF:Ag >15% and vWF:CBA >9% responded. Virtually all patients with a baseline vWF:Ag >25%, vWF:RiCoF >25% and a vWF:CBA >27% had a CR at one hour. Factor VIII levels reached normal levels in all cases regardless of vWF responses. No patient with type 2A responded, and all patients with mildly reduced RiCoF in isolation achieved CR. Nineteen patients with type 1 disease underwent testing at 24 hours. 13/15 with type 1 and a CR at one hour had adequate (>30%) levels at 24 hours. None of four patients with a PR at one hour had adequate levels at 24 hours. Median vWF:Ag and vWF:CBA levels were approximately 20% above initial levels at 24 hours in the responders. Conclusions: Patients with type 2A, and type 1 vWD with baseline vWF:Ag ≤15% and vWF:CBA ≤9% should not undergo DDAVP trial as they are unlikely to respond. Patients with type 1 vWD and baseline vWF:Ag >25%, vWF:RiCoF >25% and vWF:CBA >27%, or others with isolated low vWF:RiCoF and bleeding phenotype, need not undergo a DDAVP trial to establish efficacy. However, these patients may still require a DDAVP trial for assessment of safety and tolerability. It is not essential to measure factor VIII levels in patients who are undergoing a DDAVP trial. All patients with vWD parameters in the normal range one hour following DDAVP should be considered for further testing at 24 hours to identify the occasional suboptimal responder. Implementation of this testing strategy would reduce the requirement for DDAVP trials by approximately 35%, based upon our series.