Patricia H. Watson

Bio: Patricia H. Watson is an academic researcher from Lawson Health Research Institute. The author has contributed to research in topics: Bone disease & Blastocyst. The author has an hindex of 6, co-authored 8 publications receiving 506 citations.

A randomized controlled trial to compare the efficacy of cyclical parathyroid hormone versus cyclical parathyroid hormone and sequential calcitonin to improve bone mass in postmenopausal women with osteoporosis.

Abstract: Short cycles of human (h) PTH-(1-34) may have an anabolic effect to increase bone mass in patients with osteoporosis. As PTH also stimulates bone resorption, it is theoretically possible to enhance the anabolic effects of PTH by using a sequential antiresorptive agent in the treatment cycle. To test this hypothesis, 30 women with osteoporosis, aged 67 +/- 8 yr, completed a 2-yr protocol that comprised 28-day courses of hPTH-(1-34) (800 U) given by daily sc injections; each course was repeated at 3-month intervals. By random allocation, patients either received sequential calcitonin (CT) immediately following the cycle of hPTH-(1-34) (75 U/day, sc; PTH + CT; n = 16) or placebo CT (PTH alone; n = 14) for 42 days. Baseline bone mineral density (BMD) at the lumbar spine site revealed t scores of -3.7 +/- 1.2 (+/-SD) for the PTH alone group and -3.0 +/- 1.4 for the PTH + CT groups, who had 2.0 +/- 2.3 and 1.8 +/- 2.4 vertebral fractures, respectively, at entry to the study. At the end of the 2 yr, the lumbar spine BMD increased from 0.720 +/- 0.130 to 0.793 +/- 0.177 g/cm2 (10.2%) in the PTH group and from 0.760 +/- 0.168 to 0.820 +/- 0.149 g/cm2 (7.9%) in the PTH + CT group. These changes were significant over time in both groups (P < 0.001). Although the final 2-yr lumbar spine BMD was not significantly different between the two treatment groups, those patients receiving sequential CT injections gained bone mass at a consistently slower rate. Changes in BMD at the femoral neck averaged +2.4% and -1.8% in the PTH and PTH + CT groups, respectively, neither of which was significant. In the group receiving only cyclical hPTH-(1-34), the observed 2-yr vertebral fracture incidence was 4.5 compared to 23.0/100 patient yr in the PTH + CT group (P = 0.078). During the first two cycles, changes in biochemical markers of bone formation (serum total alkaline phosphatase, bone-specific alkaline phosphatase, and osteocalcin) and bone resorption (fasting urinary hydroxyproline and N-telopeptide excretion) were significantly increased over pretreatment values after 28 days of hPTH-(1-34) injections (P < 0.05 to P < 0.01 for both groups). Even end of cycle values remained elevated over the study baseline across time (P < 0.01). There were no significant differences for any outcome parameter between the two treatment groups. We conclude that short cycles (28 days) of daily hPTH-(1-34) injections result in significant increases in lumbar spine BMD, without significant changes in cortical bone mass at the femoral neck. Very low incident vertebral fracture rates were documented over 2 yr. However, there is no evidence that sequential antiresorptive therapy with CT is of any benefit over that conferred by cyclical PTH alone.

A growth factor phenotype map for ovine preimplantation development.

Abstract: The reverse transcription-polymerase chain reaction (RT-PCR) was used to determine the patterns of expression for several growth factor ligand and receptor genes during ovine preimplantation development. Transcripts for insulin-like growth factor (IGF)-I, IGF-II, and the receptors for insulin and IGF-I were detected throughout ovine preimplantation development from the 1-cell to the blastocyst stage. Transforming growth factor alpha (TGF alpha) transcripts were also detected throughout ovine preimplantation development. The mRNAs encoding basic fibroblast growth factor (bFGF) were detected in all stages of the ovine preimplantation embryo, although the relative abundance of this transcript consistently decreased from the 1-cell to the blastocyst stage, suggesting that it may represent a maternal transcript in early sheep embryos. Transcripts encoding ovine trophoblast protein (oTP) were detected only within blastocyst-stage embryos. Primary ovine oviduct cell cultures express the transcripts for IGF-II, IGF-I, TGF alpha, bFGF, TGF beta 1, and the receptors for insulin and IGF-I, suggesting that paracrine growth factor circuits may exist between the oviduct epithelium and the early ovine embryo. Transcripts for insulin, epidermal growth factor (EGF), and nerve growth factor (NGF) were not detected in any stage of the ovine preimplantation embryo or within the oviduct cell preparations. The expression of growth factor transcripts very early in mammalian development would predict that these molecules fulfil a necessary role(s) in supporting the progression of early embryos through the preimplantation interval. Our future efforts will be directed to understanding the nature of these putative regulatory pathways.

Preimplantation development of in vitro-matured and in vitro-fertilized ovine zygotes: comparison between coculture on oviduct epithelial cell monolayers and culture under low oxygen atmosphere.

Abstract: The roles of medium composition, serum source, embryo coculture, and culture under low O2 conditions on the development of in vitro-matured and in vitro-fertilized (IVMF) ovine zygotes were investigated in three separate experiments. In the first experiment, the proportion of cocultured IVMF zygotes developing to the blastocyst stage was significantly higher (38.0% vs. 3.5%; p < 0.05) than that of non-cocultured zygotes treated within three embryo culture media (TCM-199 + 10% fetal bovine serum [FBS]; bicarbonate-buffered, glucose-free synthetic oviduct fluid medium [mod-SOFM] + 10% FBS; and bicarbonate-buffered BSA-free Tyrode's salt solution [mod-TALP] + 10% FBS) under a 5% CO2 atmosphere in air. In a second experiment, a significantly higher (p < 0.05) proportion of cocultured zygotes placed in TCM-199 medium survived to the blastocyst stage (37.4% blastocysts vs. 23.4% in mod-SOFM). No significant effect of serum (FBS vs. human serum [HS]) was observed on embryonic development, but coculture was confirmed to exert a significant influence on development to the blastocyst stage. In the final experiment, survival of the embryo under a reduced oxygen (5% CO2:5% O2:90% N2) atmosphere was investigated. In contrast to results in the initial experiments, embryonic survival was significantly higher (p < 0.05) in the non-cocultured treatment groups (21.9% blastocysts vs. 0.4% for cocultured zygotes). Serum source also had a significant (p < 0.05) influence upon the development of non-cocultured zygotes: 32.3% of zygotes cultured with HS progressed to the blastocyst stage vs. 11.5% of zygotes cultured in FBS-supplemented medium. These results have characterized two distinct culture environments, each capable of supporting the development of high frequencies of unselected IVMF zygotes to the blastocyst stage in vitro.

Comparison of the biochemical responses to human parathyroid hormone-(1-31)NH2 and hPTH-(1-34) in healthy humans.

Abstract: The 1–31 fragment of human PTH [hPTH-(1–31)NH2] has been shown, like hPTH-(1–34), to have anabolic effects on the skeletons of ovariectomized rats when given intermittently, but, unlike hPTH-(1–34), it does so without affecting serum calcium concentrations and does not activate the protein kinase C second messenger pathway in some target cells. To investigate the biochemical responses to hPTH-(1–31) in humans, we have directly compared it to hPTH-(1–34) during the course of slow infusions of each. Ten healthy adults, five men and five women, aged 26 ± 5 yr (range, 22–37), each received 8-h continuous infusions of 8 pmol/kg·h hPTH-(1–34) and hPTH-(1–31) given in random order at least 2 weeks apart. During the infusions there were significant increases in both plasma and urinary cAMP (P < 0.05), but there were no differences in the responses between the two peptides (P = 0.362 for plasma; P = 0.987 for urine). There were also significant phosphaturic and natriuretic responses to the two peptides, which agai...

2010 clinical practice guidelines for the diagnosis and management of osteoporosis in Canada: summary

Abstract: See related commentary by Kanis, page [1829][1] Since the publication of the Osteoporosis Canada guidelines in 2002, there has been a paradigm shift in the prevention and treatment of osteoporosis and fractures. [1][2],[2][3] The focus now is on preventing fragility fractures and their negative

Oxidative stress and protection against reactive oxygen species in the pre-implantation embryo and its surroundings

Abstract: Oxidative stress is involved in the aetiology of defective embryo development. Reactive oxygen species (ROS) may originate from embryo metabolism and/or embryo surroundings. Embryo metabolism generates ROS via several enzymatic mechanisms. The relative contribution of each source seems different depending on the species, the stage of development, and the culture conditions. Several exogenous factors and culture conditions can enhance the production of ROS by embryos. ROS can alter most types of cellular molecules, and also induce development block and retardation. Multiple mechanisms of embryo protection against ROS exist, and these have complementary actions. External protection, present in follicular and tubal fluids, mainly comprises non-enzymatic antioxidants such as hypotaurine, taurine and ascorbic acid. Internal protection mainly comprises antioxidant enzymes: superoxide dismutase, glutathione peroxidase and gamma-glutamylcysteine synthetase. Transcripts encoding for these enzymes are present in the oocyte, embryo and oviduct. It may be important that these transcripts are stored during oocyte maturation in order to allow the embryo to acquire the aptitude to develop. It is now common to add antioxidant compounds to culture media. Nevertheless, maintaining the pro-oxidant-antioxidant equilibrium in embryos through such supplementation is a complex problem. Further studies are necessary to limit oxidative stress during embryo culture.

Bone mineral density thresholds for pharmacological intervention to prevent fractures

Abstract: Background: Treatment intervention thresholds for prevention of osteoporotic fractures can be derived from reports from the World Health Organization (diagnostic criteria) and National Osteoporosis Foundation (treatment criteria). It is not known how well these thresholds work to identify women who will fracture and are therefore candidates for treatment interventions. We used data from the National Osteoporosis Risk Assessment (NORA) to examine the effect of different treatment thresholds on fracture incidence and numbers of women with fractures within the year following bone mineral density measurement. Methods: The study comprised 149 524 white postmenopausal women aged 50 to 104 years (mean age, 64.5 years). At baseline, bone mineral density was assessed by peripheral bone densitometry at the heel, finger, or forearm. New fractures during the next 12 months were self-reported. Results: New fractures were reported by 2259 women, including 393 hip fractures; only 6.4% had baseline T scores of �2.5 or less (World Health Organization definition for osteoporosis). Although fracture rates were highest in these women, they experienced only 18% of the osteoporotic fractures and 26% of the hip fractures. By National Osteoporosis Foundation treatment guidelines, 22.6% of the women had T scores of 2.0 or less, or �1.5 or less with 1 or more clinical risk factors. Fracture rates were lower, but 45% of osteoporotic fractures and 53% of hip fractures occurred in these women. Conclusions: Using peripheral measurement devices, 82% of postmenopausal women with fractures had T scores better than �2.5. A strategy to reduce overall fracture incidence will likely require lifestyle changes and a targeted effort to identify and develop treatment protocols for women with less severe low bone mass who are nonetheless at increased risk for future fractures.

The Effects of Parathyroid Hormone, Alendronate, or Both in Men with Osteoporosis

Abstract: Background Because parathyroid hormone increases both bone formation and bone resorption, it is possible that combining parathyroid hormone with an antiresorptive agent will enhance its effect on bone mineral density. Methods We randomly assigned 83 men who were 46 to 85 years of age and had low bone density to receive alendronate (10 mg daily; 28 men), parathyroid hormone (40 μg subcutaneously daily; 27 men), or both (28 men). Alendronate therapy was given for 30 months; parathyroid hormone therapy was begun at month 6. The bone mineral density of the lumbar spine, proximal femur, radial shaft, and total body was measured every six months with the use of dual-energy x-ray absorptiometry. Trabecular bone mineral density of the lumbar spine was measured at base line and month 30 by means of quantitative computed tomography. Serum alkaline phosphatase levels were measured every six months. The primary end point was the rate of change in the bone mineral density at the posteroanterior spine. Results The bone...

Parathyroid hormone and teriparatide for the treatment of osteoporosis: a review of the evidence and suggested guidelines for its use.

Abstract: All therapies currently recommended for the management of osteoporosis act mainly to inhibit bone resorption and reduce bone remodeling. PTH and its analog, teriparatide [recombinant human PTH(1-34)], represent a new class of anabolic therapies for the treatment of severe osteoporosis, having the potential to improve skeletal microarchitecture. Significant reductions in both vertebral and appendicular fracture rates have been demonstrated in the phase III trial of teriparatide, involving elderly women with at least one prevalent vertebral fracture before the onset of therapy. However, there is as yet no evidence that the antifracture efficacy of PTH will be superior to the bisphosphonates, whereas cost-utility estimates suggest that teriparatide is significantly more expensive. Teriparatide should be considered as treatment for postmenopausal women and men with severe osteoporosis, as well as for patients with established glucocorticoid-induced osteoporosis who require long-term steroid treatment. Teriparatide should also be considered for the management of individuals at particularly high risk for fractures, including subjects who are younger than age 65 and who have particularly low bone mineral density measurements (T scores < or = 3.5). Teriparatide therapy is not recommended for more than 2 yr, based, in part, on the induction of osteosarcoma in a rat model of carcinogenicity. Total daily calcium intake from both supplements and dietary sources should be limited to 1500 mg together with adequate vitamin D intake (< or =1000 U/d). Monitoring of serum calcium may be safely limited to measurement after 1 month of treatment; mild hypercalcemia may be treated by withdrawing dietary calcium supplements, reducing the dosing frequency of PTH, or both. At present, concurrent therapy with antiresorptive therapy, particularly bisphosphonates, should be avoided, although sequential therapy with such agents may consolidate the beneficial effects upon the skeleton after PTH is discontinued.