Effects of Risedronate in Runx2 Overexpressing Mice, an Animal Model for Evaluation of Treatment Effects on Bone Quality and Fractures

Young mice overexpressing Runx2 specifically in cells of the osteoblastic lineage failed to gain bone mass and exhibited a dramatic increase in bone resorption, leading to severe osteopenia and spontaneous vertebral fractures. The objective of the current study was to determine whether treatment with a bisphosphonate (risedronate, Ris), which reduces fractures in postmenopausal as well as in juvenile osteoporosis, was able to improve bone quality and reduce vertebral fractures in mice overexpressing Runx2. Four-week-old female Runx2 mice received Ris at 2 and 10 μg/kg subcutaneously twice a week for 12 weeks. Runx2 and wild-type mice received vehicle (Veh) as control. We measured the number of new fractures by X-ray and bone mineral density (BMD) by DEXA. We evaluated bone quality by histomorphometry, micro-CT, and Fourier transform infrared imaging (FTIRI). Ris at 20 μg/kg weekly significantly reduced the average number of new vertebral fractures compared to controls. This was accompanied by significantly increased BMD, increased trabecular bone volume, and reduced bone remodeling (seen in indices of bone resorption and formation) in the vertebrae and femoral metaphysis compared to Runx2 Veh. At the femur, Ris also increased cortical thickness. Changes in collagen cross-linking seen on FTIRI confirmed that Runx2 mice have accelerated bone turnover and showed that Ris affects the collagen cross-link ratio at both forming and resorbing sites. In conclusion, young mice overexpressing Runx2 have high bone turnover-induced osteopenia and spontaneous fractures. Ris at 20 μg/kg weekly induced an increase in bone mass, changes in bone microarchitecture, and decreased vertebral fractures

Electrical Impedance of Acupuncture Meridians: The Relevance of Subcutaneous Collagenous Bands

Background: The scientific basis for acupuncture meridians is unknown. Past studies have suggested that acupuncture meridians are physiologically characterized by low electrical impedance and anatomically associated with connective tissue planes. We are interested in seeing whether acupuncture meridians are associated with lower electrical impedance and whether ultrasound-derived measures – specifically echogenic collagenous bands- can account for these impedance differences. Methods/Results: In 28 healthy subjects, we assessed electrical impedance of skin and underlying subcutaneous connective tissue using a four needle-electrode approach. The impedances were obtained at 10 kHz and 100 kHz frequencies and at three body sites- upper arm (Large Intestine meridian), thigh (Liver), and lower leg (Bladder). Meridian locations were determined by acupuncturists. Ultrasound images were obtained to characterize the anatomical features at each measured site. We found significantly reduced electrical impedance at the Large Intestine meridian compared to adjacent control for both frequencies. No significant decrease in impedance was found at the Liver or Bladder meridian. Greater subcutaneous echogenic densities were significantly associated with reduced impedances in both within-site (meridian vs. adjacent control) and between-site (arm vs. thigh vs. lower leg) analyses. This relationship remained significant in multivariabl

Hepatic Abnormalities Associated with Aluminum Loading in Piglets

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141476/1/jpen0293.pd

Somatostatin analogues in the treatment of gastroenteropancreatic neuroendocrine tumours, current aspects and new perspectives

Gastroenteropancreatic neuroendocrine tumours (GEP NETs) are rare tumours that present many clinical features

Gastrointestinal symptoms and association with medication use patterns, adherence, treatment satisfaction, quality of life, and resource use in osteoporosis: baseline results of the MUSIC-OS study

Summary: The Medication Use Patterns, Treatment Satisfaction, and Inadequate Control of Osteoporosis Study (MUSIC-OS) is a prospective, observational study of women with osteoporosis in Europe and Canada. At baseline, patients with gastrointestinal symptoms reported lower adherence to osteoporosis treatment, treatment satisfaction, and health-related quality of life, than those without gastrointestinal symptoms. Introduction: The aim of the study was to examine gastrointestinal (GI) symptoms and the association between GI symptoms and treatment adherence, treatment satisfaction, and health-related quality of life (HRQoL) among osteoporotic women in Europe and Canada. Methods: Baseline results are reported here for a prospective study which enrolled postmenopausal, osteoporotic women who were initiating (new users) or continuing (experienced users) osteoporosis treatment at study entry (baseline). A patient survey was administered at baseline and included the occurrence of GI symptoms during 6-month pre-enrolment, treatment adherence (adherence evaluation of osteoporosis (ADEOS), score 0–22), treatment satisfaction (Osteoporosis Treatment Satisfaction Questionnaire for Medications (OPSAT-Q), score 0–100) and HRQoL (EuroQol-5 dimension (EQ-5D) utility, score 0–1; OPAQ-SV, score 0–100). The association between GI symptoms and ADEOS (experienced users), OPSAT-Q (experienced users), and HRQoL (new and experienced users) was assessed by general linear models adjusted for patient characteristics. Results: A total of 2959 patients (2275 experienced and 684 new users) were included. Overall, 68.1 % of patients experienced GI symptoms in the past 6 months. Compared with patients without GI symptoms, patients with GI symptoms had lower mean baseline scores on most measures. The mean adjusted differences were ADEOS, −0.43; OPSAT-Q, −5.68; EQ-5D, −0.04 (new users) and −0.06 (experienced users), all P < 0.01. GI symptoms were also associated with lower OPAQ-SV domain scores: physical function, −4.17 (experienced users); emotional status, −4.28 (new users) and −5.68 (experienced users); back pain, −5.82 (new users) and −11.33 (experienced users), all P < 0.01. Conclusions: Patients with GI symptoms have lower treatment adherence and treatment satisfaction and worse HRQoL than patients without GI symptoms