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Biomedical subjects

Philip Sambrook

Publications and source records attributed to Philip Sambrook.

18 recordsLinked to original sources
PubMed2006

Osteoporosis.

Osteoporosis is a serious public health issue. The past 10 years have seen great advances in our understanding of its epidemiology, pathophysiology, and treatment, and further advances are rapidly being made. Clinical assessment will probably evolve from decisions mainly being made on the basis of bone densitometry, to use of algorithms of absolute fracture risk. Biochemical markers of bone turnover are also likely to become more widely used. Bisphosphonates will probably remain the mainstay of therapy, but improved understanding of the optimum amount of remodelling suppression and duration of therapy will be important. At the same time, other diagnostic and therapeutic approaches, including biological agents, are likely to become more widespread.

Aged↗
PubMed2006

Intravenous ibandronate injections in postmenopausal women with osteoporosis: one-year results from the dosing intravenous administration study.

OBJECTIVE: Although oral bisphosphonates are effective treatments for postmenopausal women with osteoporosis, oral dosing may be unsuitable for some patients. An efficacious intravenously administered bisphosphonate could be beneficial for such patients. Ibandronate, a potent nitrogen-containing bisphosphonate, can be administered using extended dosing intervals, either orally or by rapid intravenous injection. The aim of this study was to identify the optimal intravenous dosing regimen for ibandronate in postmenopausal women with osteoporosis. METHODS: In a randomized, double-blind, double-dummy, phase III, noninferiority study, we compared 2 regimens of intermittent intravenous injections of ibandronate (2 mg every 2 months and 3 mg every 3 months) with a regimen of 2.5 mg of oral ibandronate daily, the latter of which has proven antifracture efficacy. The study group comprised 1,395 women (ages 55-80 years) who were at least 5 years postmenopausal. All patients had osteoporosis (lumbar spine [L2-L4] bone mineral density [BMD] T score less than -2.5). Participants also received daily calcium (500 mg) and vitamin D (400 IU). The primary end point was change from baseline in lumbar spine BMD at 1 year. Changes in hip BMD and in the level of serum C-telopeptide of type I collagen (CTX) were also measured, as were safety and tolerability. RESULTS: At 1 year, mean lumbar spine BMD increases were as follows: 5.1% among 353 patients receiving 2 mg of ibandronate every 2 months, 4.8% among 365 patients receiving 3 mg of ibandronate every 3 months, and 3.8% among 377 patients receiving 2.5 mg of oral ibandronate daily. Both of the intravenous regimens not only were noninferior, but also were superior (P < 0.001) to the oral regimen. Hip BMD increases (at all sites) were also greater in the groups receiving medication intravenously than in the group receiving ibandronate orally. Robust decreases in the serum CTX level were observed in all arms of the study. Both of the intravenous regimens were well tolerated and did not compromise renal function. CONCLUSION: As assessed by BMD, intravenous injections of ibandronate (2 mg every 2 months or 3 mg every 3 months) are at least as effective as the regimen of 2.5 mg orally daily, which has proven antifracture efficacy, and are well tolerated.

Administration, Oral↗
PubMed2006

Compliance with treatment in osteoporosis patients--an ongoing problem.

BACKGROUND: Osteoporosis is a chronic condition that generally requires long term therapy with agents such as bisphosphonates, selective oestrogen receptor modulators, or hormone therapy for fracture risk reduction to be apparent. However, compliance with therapy in the 'real world' setting has generally been less than that seen in clinical trials. OBJECTIVE: This article reviews the trends of compliance and persistence with bisphosphonate therapy in patients with osteoporosis in the 'real world' setting. DISCUSSION: Studies in Australia and overseas have shown that once weekly administration of bisphosphonates improves compliance with treatment compared with a daily regimen. However, although patients prefer once weekly bisphosphonates over daily treatment, compliance and persistence remained suboptimal in many patients receiving once weekly therapy. The introduction of less frequent dosing regimens such as once monthly or once yearly may increase compliance.

Australia↗
PubMed2006

Longterm effects of intraarticular hyaluronan on synovial fluid in osteoarthritis of the knee.

OBJECTIVE: Intraarticular (IA) hylan injections constitute second-line therapy for osteoarthritis (OA) of the knee, but human studies suggesting a possible mechanism of action are lacking. We examined the effect of IA Hylan GF-20 injections on synovial fluid (SF) hyaluronan (HA) concentration, viscosity, and elasticity over a 6-month period in patients with mild to moderate OA of the knees. METHODS: Patients with symptomatic knee OA (Osteoarthritis Research Society International grade 1-2) had SF aspirated from the study knee pre- and 3 and 6 months post-Hylan injection. Primary endpoints included SF HA concentration, viscosity, and elasticity. SF HA concentration was determined using uronic acid assay, and rheology measured using a micro-Fourier rheometer. RESULTS: Sequential SF samples were available from 32 of 60 subjects injected at baseline (15 men, 17 women; mean age 65 yrs) at 3 months post-injection. The mean HA concentration had increased by 13% (p<0.0008), and the complex shear modulus had increased by 16% (p<0.03). Sufficient SF was also available from 19 of these subjects at 6 months post-injection when mean HA concentration was 2.24+/-0.62 mg/ml compared to their baseline mean of 2.02+/-0.52 mg/ml, an increase of 10% (p<0.053). CONCLUSION: This open-label study showed a statistically significant change from baseline in both SF HA concentration and complex shear modulus at 3 months following IA Hylan GF-20 injection among subjects with mild to moderate knee OA. These results suggest that one possible mechanism of action of viscosupplementation is to promote endogenous HA production. Longer-term studies are required to identify whether these changes in SF measures are important for modification of disease progression in knee OA.

Adult↗
PubMed2006

Bisphosphonates and osteonecrosis of the jaw.

Recently an association between bisphosphonate use and a rare dental condition termed 'osteonecrosis of the jaw' (ONJ) has been reported. Patients with osteoporosis and Paget disease who take bisphosphonates have a significantly reduced risk of fracture and other skeletal complications. This represents significant health benefits, against which the small risk of ONJ needs to be considered. In patients with bone malignancy, the risk of ONJ needs to be balanced against the benefit of therapy on the underlying malignancy. There are still many uncertainties about this condition. This position paper seeks to summarise what is currently known about ONJ to provide information to medical practitioners and dental practitioners.

Bone Neoplasms↗
PubMed2005

Comparison of serum FSH and Inhibin B levels between adult male dizygotic and monozygotic twins.

BACKGROUND: FSH hypersecretion occurs in mothers of dizygotic (DZ) twins. Twinning is inherited via both sexes and transmitted through the female. FSH hypersecretion may thus occur in male DZ twins. METHODS: We assayed FSH and its counter-regulatory hormone, Inhibin B, in 108 adult male DZ and 100 monozygotic (MZ) twins (as controls) and compared our results to published norms. RESULTS: Inhibin B was elevated and higher in DZ compared with MZ twins with similar FSH. CONCLUSION: The normal FSH: Inhibin B endocrine feedback axis is different in adult male DZ twins. This contributes to the theory that the answer to human DZ twinning lies in the actions of FSH and Inhibin, and in their mutual interaction.

Adult↗
PubMed2005

Gender differences in relationships between body composition components, their distribution and bone mineral density: a cross-sectional opposite sex twin study.

Numerous studies indicate that bone mineral density (BMD) is closely related to body mass and its components. Most studies have examined these relationships in women with little attention given to how these relationships differ by gender. The aims of the present study were to use the opposite sex twin model to determine if there were gender differences in the relationship between body composition and its relation to BMD and how any such differences were influenced by age. We measured body composition and bone mass by dual energy X-ray absorptiometry in 93 pairs of opposite sex twins. To examine the effect of age, they were divided into two age groups: under 50 years old (45 pairs) and over 50 years old (48 pairs). Lean mass (LM) had stronger positive relationships with the most bone variables than fat mass in both genders at all ages. Fat mass (FM) had positive relationships with total body and hip BMD in women under age 50, but not over 50. There was no significant relationship between FM and total or regional BMD in men under age 50, but men over 50 showed positive relationships between FM measures and total and some regional BMD measures. Central adiposity showed a positive relationship with BMD in men over 50 and women under 50. Fat mass (FM) and lean mass (LM) and their distribution in the body have different relationships with regional BMD in men and women that differ by age.

Absorptiometry, Photon↗
PubMed2005

Who will benefit from treatment with selective estrogen receptor modulators (SERMs)?

Clinical trials have demonstrated that the selective estrogen receptor modulator raloxifene can reduce the risk of vertebral fracture, but have not unequivocally demonstrated an effect on non-vertebral fracture. Consequently it is recommended that raloxifene be used mainly in postmenopausal women with milder osteoporosis as a preventive measure or for treatment in those with predominantly spinal osteoporosis. Since the effects of raloxifene on bone mineral density and bone turnover may reverse soon after cessation, it is recommended that raloxifene be used as long-term therapy for 5-10 years. Because of its quicker offset, use of raloxifene may have advantages over potent bisphosphonates if use of anabolic agents are contemplated in an individual patient.

Aged↗
PubMed2004

Management of bone loss after organ transplantation.

Organ transplant recipients experience rapid bone loss and high fracture rates, particularly during the early post-transplant period. Early rapid bone loss occurs in the setting of uncoupled bone turnover with increased bone resorption and decreased bone formation. Because there are no clinical factors that reliably predict post-transplant bone loss and fractures in the individual patient, all transplant recipients should be considered candidates for early preventive therapy for osteoporosis. Long-term transplant recipients with densitometric osteoporosis and/or fractures should also receive treatment. Although active metabolites of vitamin D and bisphosphonates have both shown efficacy, data from clinical trials suggest that bisphosphonates are the safest and most consistently effective agents for the prevention and treatment of post-transplantation osteoporosis in adults. Kidney transplant recipients represent a special population, and more research is needed to delineate the risks and benefits of treating bone disease in these patients.

Bone Density↗
PubMed2004

Guidelines for the management of postmenopausal osteoporosis for GPs.

BACKGROUND: Since the last series of guidelines on the management of osteoporosis from Osteoporosis Australia was published in Australian Family Physician (October 2002), there have been further advances in our understanding of the treatment involved in both the prevention of bone loss and the management of established osteoporosis. OBJECTIVE: This article provides updated guidelines for the management of postmenopausal osteoporosis to assist general practitioners identify those women at risk, and reviews current treatment strategies. DISCUSSION: Osteoporosis and its associated problems are major health concerns in Australia, especially with an aging population. While important principles of management are still considered to be maximising peak bone mass and preventing postmenopausal bone loss, new clinical trial data about drugs such as the bisphosphonates, raloxifene and oestrogen have recently become available and the relative role of various agents is gradually becoming clearer. The use of long term hormone therapy has mixed risks and benefits that requires individual patient counselling.

Absorptiometry, Photon↗
PubMed2003

Gender differences in volumetric bone density: a study of opposite-sex twins.

Gender difference in bone size is a potential confounder when comparing bone density between males and females. A comparison of volumetric BMD (vBMD) between men and women, which is a measure of bone mass relative to three-dimensional bone volume (g/cm(3)) as opposed to areal bone density (g/cm(2)), may be a more accurate reflection of gender differences in bone density. The aims of this study were to examine gender differences in bone mass (BMC), areal BMD (aBMD), volumetric BMD (vBMD) by comparing twins of opposite sex in whom the effects of age, genes and environment are partially controlled for. DEXA derived BMC, aBMD, vBMD at the third lumbar vertebra (L3), femoral neck (FN) and forearm (1/3 radius) were compared between 82 opposite sex pairs aged 18-80. BMC was significantly higher in males at all three sites (26-45.5%). For aBMD the gender differences remained significant at all sites except the spine. The average differences in aBMD were not as great as the differences in BMC (2.2-20.5%). The differences in vBMD, however, followed a different pattern. FN and L3 vBMD were significantly higher in females (4.8 and 0.6%, respectively), while radial BMD was not significantly different between the sexes. Comparing aBMD values between males and females, when females in general have a smaller skeleton than males may not be a true indication of gender differences in bone density. A comparison of vBMD between men and women shows only small differences in bone density between the sexes.

Adult↗
PubMed2003

Once weekly alendronate.

Alendronate, a bisphosphonate that potently inhibits bone resorption, has been shown in long-term clinical trials to be an effective treatment for osteoporosis, increasing bone mineral density and substantially reducing the incidence of both vertebral and nonvertebral fractures, including hip fractures, mostly using a daily dosage regimen. Although daily administration has generally been well tolerated in these trials, some patients develop upper gastrointestinal symptoms. Current safety and efficacy data suggest that once-weekly dosing of alendronate appears to be as efficacious as daily administration in the treatment of osteoporosis, providing greater convenience to patients, improved compliance and a lower risk of upper gastrointestinal symptoms compared with daily administration. This review examines published data addressing the safety and efficacy of once-weekly alendronate administration.

Alendronate↗
PubMed2002

Gender differences in the genetic factors responsible for variation in bone density and ultrasound.

Although genetic factors are thought to explain a large proportion of the variation in bone density in women, few studies have been conducted in men. Therefore, it is unclear whether the individual differences in bone strength between men and women are a reflection of gender differences in the relative influence of genetic and environmental factors on bone density variance. The aim of this study was to determine if there were gender differences in the genetic components of variance for bone density and ultrasound. In addition, the study aimed to explore the hypothesis that there are unique gender-specific genetic determinants of these traits. Bone mineral density (BMD) of the hip, distal forearm, and lumbar spine were measured by dual-energy X-ray absorptiometry (DXA) as well as quantitative ultrasound (QUS) at the calcaneus in healthy female twin pairs (286 identical [MZ] and 265 nonidentical [DZ]), male twin pairs (72 MZ and 65 DZ), and 82 opposite-sex (OS) pairs aged between 18 and 80 years. For hip BMD, distal forearm, and QUS measurements, the differences between MZ correlations and like-sex DZ correlations were similar for both sexes, suggesting little difference in the component of total variance explained by genetic factors between male and female twin pairs. However, correlations between OS twin pairs were lower than that of like-sex twin pairs, suggesting the possibility of unique gender-specific genetic effects. At the forearm, model fitting suggested a small gender difference in the magnitude of genetic variance as well as the presence of a unique gender-specific genetic variance component. Hip, lumbar spine, and QUS measurements were better explained by models that assumed no gender differences in genetic variance between the sexes, but the study had insufficient power to detect small differences in the genetic components of variance. The results of this study suggest that the proportion of bone strength variance explained by genetic factors is similar for men and women. However, at some regions there is evidence to suggest a gender-specific genetic component to the overall genetic variance.

Absorptiometry, Photon↗
PubMed2002

Guidelines for the treatment of postmenopausal osteoporosis for general practitioners.

BACKGROUND: Osteoporosis Australia has been committed to the education of general practitioners and the community with a series of updated guidelines on the management of osteoporosis. Since the last series was published in Australian Family Physician (August 2000), there have been further advances in our understanding of the treatments involved in both prevention of bone loss and the management of established osteoporosis. OBJECTIVE: This article represents updated guidelines for the treatment of postmenopausal osteoporosis to assist GPs identify those women at risk and to review current treatment strategies. DISCUSSION: Osteoporosis and its associated problems are major health concerns in Australia, especially with an aging population. While important principles of management are still considered to be maximising peak bone mass and preventing postmenopausal bone loss, new clinical trial data about drugs such as the bisphosphonates, raloxifene and oestrogen have recently become available and the relative role of various agents is gradually becoming clearer. The use of long term hormone replacement therapy has mixed risks and benefits that requires individual patient counselling.

Australia↗
PubMedDate not supplied

Activated protein C prevents inflammation yet stimulates angiogenesis to promote cutaneous wound healing.

Activated protein C (APC) is a serine protease that plays a central role in physiological anticoagulation, and has more recently been shown to be a potent anti-inflammatory mediator. Using cultured human cells, we show here that APC up-regulates the angiogenic promoters matrix metalloproteinase-2 in skin fibroblasts and umbilical vein endothelial cells, vascular endothelial growth factor in keratinocytes and fibroblasts, and monocyte chemoattractant protein-1 in fibroblasts. In the chick embryo chorioallantoic membrane assay, APC promoted the granulation/remodeling phases of wound healing by markedly stimulating angiogenesis as well as promoting reepithelialization. In a full-thickness rat skin-healing model, a single topical application of APC enhanced wound healing compared to saline control. APC-treated wounds had markedly more blood vessels on day 7 and a significantly lower infiltration of neutrophils at days 4 and 7. The broad spectrum matrix metallo-proteinase, GM6001, prevented the ability of APC to promote wound healing. In summary, our results show that APC promotes cutaneous wound healing via a complex mechanism involving stimulation of angiogenesis and inhibition of inflammation. These unique properties of APC make it an attractive therapeutic agent to promote the healing of chronic wounds.

Animals↗