Papers by Rosemary Hannon
Journal of Bone and Mineral Research, 2008
Bone, 2006
Early response of circulating OPG to bisphosphonates has not been observed in vivo. The aim of th... more Early response of circulating OPG to bisphosphonates has not been observed in vivo. The aim of this study was to investigate the response, including the very early response, of plasma OPG and the bone resorption marker C terminal crosslinked telopeptides of Type I collagen (hCTX) to zoledronic acid in patients with metastatic bone disease. Methods: Twenty four patients (9 males, 15 females), aged 44–76 years, with advanced solid cancer and bone metastases, who had not been previously treated with bisphosphonate, were infused with a single infusion of 4 mg zoledronic acid. Blood samples were collected before 10.00 after an overnight fast at baseline, prior to infusion, and on days 1, 2, 7 and 21 after infusion. Plasma was stored at –80-C until analysis. Plasma levels of hCTX were measured by electrochemiluminescent assay. Plasma levels of OPG were measured by ELISA. Results: A significant increase in plasma OPG was detected at day 2, but not at day 7 or 21 (see table). h CTXwas significantly decreased (P < 0.0001) from day 1 (median 67%) until the end of the study ( 77%).
Proceedings of the Nutrition Society, 2011
Journal of Bone and Mineral Research, 2003
The effect of season on bone turnover is controversial. No information is available on seasonalit... more The effect of season on bone turnover is controversial. No information is available on seasonality of new serum markers of bone resorption. In this study, we have been unable to confirm findings of a marked wintertime increase in bone formation and resorption within the general population. Seasonality was assessed by cosinor analysis. We investigated the effect of season on seven markers of bone turnover in a longitudinal study (six men and six premenopausal women; age, 24-44 years) and a separate large population-based multicenter European study (n = 2780 women, Osteoporosis and Ultrasound Study [OPUS]). Measurements included serum Crosslaps, procollagen type I N-terminal propeptide (PINP), osteocalcin (OC), and the N-telopeptide fragment of type I collagen in urine (NTX). Seasonality was assessed by cosinor analysis with Hotelling&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s T2 test. Serum 25(OH) vitamin D showed a marked seasonal rhythm. There was no significant seasonal component for any marker of bone turnover in the longitudinal analysis (cosinor analysis, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 0.05). The percentage of within subject variance accounted for by any seasonal trend was very small for all markers (less than 2.5%). Less than 1% of the between-person variance was accounted for by seasonality in the cross-sectional analysis for all markers (n = 2780). There was a small but statistically significant summertime increase in OC and PINP in the healthy postmenopausal population after exclusions based on disease or medication use (remaining n = 1226, amplitudes 5.6% and 5.4%, respectively, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). We have been unable to confirm findings of a marked wintertime increase in bone formation and resorption within the general population. The absence of marked seasonality was irrespective of age, menopausal status, reported supplemental Vitamin D intake, age or geographical location. The small but statistically significant summertime increase in bone formation in this and other studies is unlikely to confound clinical interpretation of these measurements.
Journal of Bone and Mineral Research, 1999
... Adriana Braga De castro machado,; Rosemary Hannon,; Prof. ... I collagen (NTX) (Osteomark; Os... more ... Adriana Braga De castro machado,; Rosemary Hannon,; Prof. ... I collagen (NTX) (Osteomark; Ostex International Inc., Seattle, WA, USA) with an intra-assay coefficient of variation (CV) of 8%, immunoreactive free deoxypyridinoline (iFDpd) (Pyrilinks-D assay; Metra Biosystems Inc ...
Bone, 2002
Bone turnover markers are subject to day-to-day and within-day variability, which may influence c... more Bone turnover markers are subject to day-to-day and within-day variability, which may influence clinical interpretation. We examined the effect of fasting vs. feeding on the concentration and between-day variability of several markers. Twenty healthy premenopausal women were studied on 10 consecutive weekdays. Subjects were studied either in the fasting (no breakfast) or fed (breakfast at 08:00 h) state on alternate days, and were randomized to begin either fasting or fed. Two hour urine collections were obtained each day between 08:00 h and 10:00 h, and blood samples were collected daily at 09:00 h. The N-telopeptide cross-link of type I collagen in urine (uNTX) and serum (sNTX), the C-telopeptide in urine (uCTX) and serum (sbetaCTX), and immunoreactive free deoxypyridinoline (uifDPD) in urine were measured as resorption markers. Procollagen type I N-terminal propeptide (PINP), osteocalcin (OC), and bone alkaline phosphatase (bone ALP) were measured as formation markers. All bone formation and resorption markers were significantly lower in the fed state with the exception of bone ALP. The magnitude of the decrease ranged from 3.8 +/- 0.9% for PINP (p &lt; 0.0001) to 17.8 +/- 2.6% (p &lt; 0.0001) for sbetaCTX. Measurement variability was partitioned into analytical variability based on replicate assays (CV(a)) and within-subject variability (CV(i)). The CV(i) was greater (p &lt; 0.05) for some markers in the fasting state (uifDPD, uNTX, and sNTX) but greater in the fed state for other markers (OC and sbetaCTX). In conclusion, the clinical impact of feeding vs. fasting is small with the exception of sbetaCTX; however, in clinical practice, collection of samples in the fasting state may be necessary to minimize the unpredictable effects of feeding. The mechanism of the acute effect of feeding on bone turnover remains uncertain.
Bone, 2012
Saracatinib (AZD0530) is an orally active once-daily Src kinase inhibitor which modulates key sig... more Saracatinib (AZD0530) is an orally active once-daily Src kinase inhibitor which modulates key signaling pathways in cancer cells. In a Phase I study in patients with advanced solid malignancies resistant to standard treatment we assessed the effect of saracatinib on bone turnover. Fifty-one patients were randomized into three parallel groups to receive saracatinib 50, 125 or 175 mg/day. After a single dose followed by a 7-day washout, patients received once-daily doses for 21 days. Bone turnover markers were measured in serum and urine samples collected before dosing on days 1, 2, 3, 17 and 28. Samples were available at baseline and more than one other time point for 44 patients. Bone resorption markers were significantly decreased by saracatinib. Serum cross-linked C-terminal telopeptide of type I collagen (sCTX) changed in the 50, 125 and 175 mg/day groups by -36% (95% CI -58, -4), -64% (95% CI -75, -48) and -75% (95% CI -83, -61), respectively, at day 28. Urinary cross-linked N-terminal telopeptide of type I collagen/creatinine ratio (uNTX/Cr) changed in the 50, 125 and 175 mg/day groups by; -13% (95% CI -33, 13), -48% (95% CI -59, -34) and -50% (95% CI -62, -35), respectively, at day 28. The significant decreases in bone resorption markers indicate that suppression of Src kinase inhibits osteoclast activity in patients with advanced cancer. This result suggests that saracatinib may have therapeutic benefit in metastatic bone disease.
Annals of Medicine, 1993
In this article we review the biochemical basis for markers of bone metabolism and comment on the... more In this article we review the biochemical basis for markers of bone metabolism and comment on their bone specificity and representativeness for bone tissue. Major developments have recently taken place particularly with respect to markers of bone collagen metabolism; accordingly, they are in the focus of this review. We also attempt to relate the various collagenous and non-collagenous markers to each other and to the phases of the osteoblast phenotype.
Bone, 1995
679~95 urinary excretion of pyridinium crosslinks, measured by HPLC. Bone formation was assessed ... more 679~95 urinary excretion of pyridinium crosslinks, measured by HPLC. Bone formation was assessed by serum osteocalcin (RIA) and bone-specific alkaline phosphatase (by ~,vheat germ lectin precipitation and by immunoradiometric assay). The markers of bone resorption were higher in myeloma than in controls (9 fold in men, 4 fold in women, p<0.001). The markers of bone formation were higher in myeloma than in controls (2 fold in men only, p<0.001). In conclusion, markers of bone resorption and formation were both increased in myeloma. The bone loss in this condition may result from the relatively great increase in bone resorption as compared to bone formation. P44. Joint laxity in parents of children with temporary brittle bone disease
British Menopause Society Journal
Increased bone turnover in the postmenopausal years is a major factor in the development of osteo... more Increased bone turnover in the postmenopausal years is a major factor in the development of osteoporosis. Biochemical markers of bone turnover represent a non-invasive, repeatable and relatively inexpensive method of assessing bone turnover. Evidence to date suggests that the most useful role for these markers in the management of individual postmenopausal women will be to monitor early response to preventative therapy or treatment for established osteoporosis.
Journal of Bone and Mineral Research, 2007
Journal of Bone and Mineral Research the Official Journal of the American Society For Bone and Mineral Research, Jun 1, 2003
Changes in the level of biochemical markers of bone resorption with risedronate treatment for ost... more Changes in the level of biochemical markers of bone resorption with risedronate treatment for osteoporosis were examined as a surrogate for the decrease in fracture risk. Greater decreases in bone resorption markers were associated with greater decreases in vertebral (and nonvertebral) fractures. Antifracture efficacy of antiresorptive therapies is only partially explained by increases in bone mineral density. Early decreases in bone resorption may also play a role. We tested this hypothesis by measuring two bone resorption markers, the C-telopeptide of type I collagen (CTX) and the N-telopeptide of type I collagen (NTX), in osteoporotic patients in risedronate vertebral fracture trials. We studied 693 women with at least one vertebral deformity (mean age, 69 +/- 7 years) who received calcium (and vitamin D if required) and placebo or risedronate 5 mg daily for 3 years. The reductions in urinary CTX (median, 60%) and NTX (51%) at 3-6 months with risedronate therapy were significantly associated (p &lt; 0.05) with the reduction in vertebral fracture risk (75% over 1 year and 50% over 3 years). The changes in both CTX and NTX accounted for approximately one-half (CTX, 55%; NTX, 49%) of risedronate&#39;s effect in reducing the risk of vertebral fractures in the first year and approximately two-thirds (CTX, 67%; NTX, 66%) over 3 years compared with placebo. The changes in CTX and NTX accounted for 77% and 54%, respectively, of risedronate&#39;s effect in reducing the risk of nonvertebral fractures over 3 years compared with placebo. The relationships between vertebral fracture risk and changes from baseline in CTX and NTX were not linear (p &lt; 0.05). There was little further improvement in fracture benefit below a decrease of 55-60% for CTX and 35-40% for NTX. The decrease in bone resorption in patients taking risedronate accounts for a large proportion of the reduction in fracture risk. There may be a level of bone resorption reduction below which there is no further fracture benefit.
Bone, 2011
Background: ABCSG-12 examined the efficacy of tamoxifen (TAM) or anastrozole (ANA) ± zoledronic a... more Background: ABCSG-12 examined the efficacy of tamoxifen (TAM) or anastrozole (ANA) ± zoledronic acid (ZOL) in premenopausal patients with endocrine-responsive early breast cancer (EBC) receiving ovarian suppression with goserelin. Results at 48 months showed that Conflict of interest statement: Dr. Gnant reports receiving research support.
Journal of Bone and Mineral Research the Official Journal of the American Society For Bone and Mineral Research, Aug 1, 2006
Aromatase inhibitors reduce estrogen levels in postmenopausal women with breast cancer. Residual ... more Aromatase inhibitors reduce estrogen levels in postmenopausal women with breast cancer. Residual estrogen is an important determinant of bone turnover. Adjuvant anastrozole was associated with significant BMD loss and increased bone remodeling, whereas tamoxifen reduced bone marker levels. Introduction: In the Anastrozole, Tamoxifen, Alone or in Combination (ATAC) trial after a median followup of 68 months, a significant improvement in disease-free survival was observed with anastrozole treatment (hazard ratio [HR], 0.87; 95% CI, 0.78-0.97; p ס 0.01). Anastrozole was also associated with tolerability benefits compared with tamoxifen, but with higher fracture rates. The HR of anastrozole compared with tamoxifen after 60 months of treatment was 1.49 (95% CI, 1.25-1.77). Materials and Methods: This prospectively designed subprotocol (n ס 308) of ATAC assessed changes in BMD and bone turnover markers in postmenopausal women with invasive primary breast cancer receiving anastrozole 1 mg/day, tamoxifen 20 mg/day, or combination treatment with both agents for 5 years. Patients with osteoporosis were excluded (osteopenia permitted at the investigators discretion). Lumbar spine and total hip BMD was assessed at baseline and after 1 and 2 years; bone turnover markers (serum C-telopeptide, urinary N-telopeptide [NTX], free deoxypyridinoline, serum procollagen type-1 N-propeptide, bone alkaline phosphatase [ALP]) were assessed at baseline and after 3, 6, and 12 months. Results were expressed as median percentage change. Results: After 2 years of anastrozole treatment, BMD was lost at lumbar spine (median 4.1% loss) and total hip (median 3.9% loss) sites; increases of 2.2% and 1.2%, respectively, were observed with tamoxifen. After 1 year of anastrozole treatment, increased bone remodeling was observed (NTX, +15%; 95% CI, 3-25%; bone ALP, +20%; 95% CI, 14-25%); decreased bone remodeling was observed with tamoxifen (NTX, −52%; 95% CI, −62% to −33%; bone ALP, −16%; 95% CI, −24% to −11%). Conclusions: Anastrozole is associated with significant BMD loss and a small increase in bone turnover, whereas tamoxifen (and the combination) is associated with increased BMD and decreased remodeling. These data may explain the increased fracture risk observed with anastrozole treatment in the ATAC trial. The impact of anastrozole on bone should be weighed against its overall superior efficacy and tolerability as observed in the main ATAC trial.
Treatment of the Postmenopausal Woman, 2007
Clinical chemistry, 1995
... Apparent Instability of Osteocalcin in Serum as Measured with Different Commercially Availabl... more ... Apparent Instability of Osteocalcin in Serum as Measured with Different Commercially Available Immunoassays, Aubrey Blumsohn, Rosemary A. Hannon ... assays could relate to differences in the immunorecognition of OC fragments, the presence of other cross-reacting mole ...
Clinical Breast Cancer, 2014
In this phase II trial, the efficacy and safety of loading-dose I.V. ibandronate in patients with... more In this phase II trial, the efficacy and safety of loading-dose I.V. ibandronate in patients with breast cancer with bone metastases were evaluated. Thirty-four patients were randomized to receive a loading dose of 12 mg I.V. ibandronate on day 1 then oral ibandronate 50 mg daily (arm A), or standard oral therapy of 50 mg ibandronate daily from day 1 (arm B). The primary end point was percentage change in serum C-terminal crosslinking telopeptide of type I collagen (S-CTX) from baseline by day 5 of study. Secondary/exploratory end points included percentage change in other bone turnover markers (N-terminal cross-linking telopeptides of type I collagen [NTX], procollagen type I N propeptide, bone alkaline phosphatase) and change in average bone pain score. There was a significantly greater reduction in S-CTX at day 5 in arm A compared with arm B (median difference, 15.82%; P = .005). There was also a significantly greater reduction in urine NTX/creatinine at day 5 (P = .009) and at the end of weeks 1 to 8 (averaged; P = .006). Average bone pain score was lower in arm A at the end of 8 weeks (P = .012). There were no additional adverse events after administration of 12 mg I.V. loading dose of ibandronate. A 12-mg dose of I.V. ibandronate rapidly reduced markers of bone turnover and can be administered without additional toxicity.
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Papers by Rosemary Hannon