Papers by Louis-georges Ste-marie
Changes of the bone formation marker PINP correlated positively with improvements in vertebral st... more Changes of the bone formation marker PINP correlated positively with improvements in vertebral strength in men with glucocorticoid-induced osteoporosis (GIO) who received 18-month treatment with teriparatide, but not with risedronate. These results support the use of PINP as a surrogate marker of bone strength in GIO patients treated with teriparatide. Introduction To investigate the correlations between biochemical markers of bone turnover and vertebral strength estimated by finite element analysis (FEA) in men with GIO.
Changes of the bone formation marker PINP correlated positively with improvements in vertebral st... more Changes of the bone formation marker PINP correlated positively with improvements in vertebral strength in men with glucocorticoid-induced osteoporosis (GIO) who received 18-month treatment with teriparatide, but not with risedronate. These results support the use of PINP as a surrogate marker of bone strength in GIO patients treated with teriparatide. Introduction To investigate the correlations between biochemical markers of bone turnover and vertebral strength estimated by finite element analysis (FEA) in men with GIO.
American journal of kidney diseases : the official journal of the National Kidney Foundation, Jan 2, 2015
Teriparatide, a recombinant form of parathyroid hormone, is an anabolic agent approved for use in... more Teriparatide, a recombinant form of parathyroid hormone, is an anabolic agent approved for use in women and men with osteoporosis. However, it is not well studied in people with chronic kidney disease (CKD). We report on a patient with stage 5 CKD treated with dialysis who presented to our clinic with multiple fractures, including bilateral nondisplaced pelvic fractures resulting in chronic pain and interfering with the patient's ability to work. Bone histomorphometry demonstrated low-turnover bone disease, and he was treated with 20μg of teriparatide (subcutaneous injection) every morning for 24 months. Within 6 months of initiating therapy, the patient's pain resolved and he was able to resume work. Serum calcium and phosphate levels remained within reference ranges throughout his treatment, and he sustained no further fractures. During 24 months of treatment, bone mineral density was maintained at the lumbar spine, and there was an increase of 4% at the femoral neck and t...
• Compliance with alendronate and risedronate is suboptimal. • Few studies have specifically eval... more • Compliance with alendronate and risedronate is suboptimal. • Few studies have specifically evaluated the impact of noncompliance with alendronate or risedronate on the incidence of osteoporotic fractures in community-dwelling elderly women.
It has been established that women who have had a first osteoporotic fracture are at a significan... more It has been established that women who have had a first osteoporotic fracture are at a significantly greater risk of future fractures. Effective antiresorptive treatments (ART) are available to reduce this risk, yet little information is available on trends in ART drug use among the elderly. The objective is to estimate the rate ratio (RR) of having an ART prescription filled among elderly women and its relation to selected determinants from 1995 through 2001. A cohort design was used. Through random sampling, we selected 40% of the women aged 70 years and older listed in the Régie de l'assurance maladie du Québec (RAMQ) health database. The women were grouped into four cohorts (for 1995, 1996, 1998 and 2000). January 1 was established as the index date within each cohort (1995, 1996, 1998 and 2000). The dependent variable was the RR of having at least one prescription of ART drugs filled during the year following the index date among women with and without prior use. ART users were divided in two groups: bone-specific drugs (bisphosphonates, calcitonin, raloxifen) and HRT (hormone replacement therapy). The independent variable was whether or not (control) there had been an osteoporotic-related fracture. The RR was determined for having at least one prescription of bone-specific drugs or of HRT filled during the year following the index date using a Cox regression adjusted for age, chronic disease score (CDS) and prior bone mineral density (BMD) test. Crude rates of BMD testing (per 500 person-years) ranged from 20.4 (1995) to 41.1 (2000) in women who had had an osteoporotic-related fracture, and from 4.4 to 15.3 in controls. The crude rate of women (per 100 person-years) who had had an osteoporotic-related fracture and who took at least one bone-specific drug during follow-up ranged from 1.9 in 1995 to 31 in 2000 among those with prior osteoporotic-related fracture, and from 0.5 in 1995 to 11 in 2000 for controls; the corresponding figures for HRT ranged 6.7 in 1995 to 13 in 2000, and from 8.4 in 1995 to 11 in 2000 respectively. BMD test is the only major factor affecting the adjusted RR of having a prescription filled for bone-specific drugs (RR of 10.44; 6.91-15.79 in 1995 and RR of 3.68; 3.30-4.10 in 2000) or HRT (RR of 2.08; 1.64-2.64 in 1995 and RR of 1.44; 1.17-1.77 in 2000), particularly among women who had not had prior use. The fact of having a fracture status does significantly affect the RR of having at least one bone-specific drug prescription filled only among women without prior use (RR of 1.71; 1.26-2.33 in 1996 and RR of 1.77; 1.44-2.19 in 2000). The fact of being younger did not affect the RR of having at least one prescription of bone-specific drugs filled, but being younger increased the RR of filling a prescription of HRT. Significant change was seen over time in the number of BMD tests ordered and ART use. Effective osteoporosis interventions are not optimal in the treatment of elderly women in a Canadian health-care system who have had an osteoporotic fracture, given that approximately 25% of women who had had an osteoporotic-related fracture were users of ART.
Dihydroxyvitamin D has potent antiproliferative and anti-invasive properties in vitro in cancer c... more Dihydroxyvitamin D has potent antiproliferative and anti-invasive properties in vitro in cancer cells. However, its calcemic effect in vivo limits its therapeutic applications. Here, we report the efficacy of EB 1089, a low calcemic analogue of vitamin D, on the development of osteolytic bone metastases after intracardiac injection of the human breast cancer cell line MDA-MB-231 in nude mice. Animals
Seminars in Arthritis and Rheumatism, 2000
Objectives: To educate scientists and health care providers about the effects of corticosteroids ... more Objectives: To educate scientists and health care providers about the effects of corticosteroids on bone, and advise clinicians of the appropriate treatments for patients receiving corticosteroids. Methods: This review summarizes the pathophysiology of corticosteroidinduced osteoporosis, describes the assessment methods used to evaluate this condition, examines the results of clinical trials of drugs, and explores a practical approach to the management of corticosteroid-induced osteoporosis based on data collected from published articles. Results: Despite our lack of understanding about the biological mechanisms leading to corticosteroid-induced bone loss, effective therapy has been devei= oped. Bisphosphonate therapy is beneficial in both the prevention and treat= ment of corticosteroid-induced osteoporosis. The data for the bisphosphonates are more compelling than for any other agent. For patients who have been treated but continue to lose bone, hormone replacement therapy, calcitonin, fluoride, or anabolic hormones should be considered. Calcium should be used only as an adjunctive therapy in the treatment or prevention of corticosteroidinduced bone loss and should be administered in combination with other agents.
Osteoporosis Research, 2011
Animal models are essential for preclinical skeletal research, notably in the study of physiopath... more Animal models are essential for preclinical skeletal research, notably in the study of physiopathology of metabolic bone diseases as well as in the evaluation of a test agent for the prevention and treatment of bone diseases such as osteoporosis. However, rat or mouse models do not completely reflect human bone disorders and therapeutic responses, but they provide insight into the
Bone, 2007
Hypocalcemia secondary to vitamin D3 (D3) depletion (D−Ca−) perturbs extra- and intracellular cal... more Hypocalcemia secondary to vitamin D3 (D3) depletion (D−Ca−) perturbs extra- and intracellular calcium (Ca). To study the effect of cyclic nutritional changes in the D3 and calcium (Ca) repletion state, we investigated the lasting effects of calcium or D3 repletion on calcium and bone metabolism using a novel depletion–repletion–redepletion protocol. D−Ca− rats presenting osteomalacia without rickets and a significant impairment
Journal of Histochemistry & Cytochemistry, 2004
SUMMARY Methylmethacrylate (MMA) embedding is routinely used for histomorphome- try of undecalcif... more SUMMARY Methylmethacrylate (MMA) embedding is routinely used for histomorphome- try of undecalcified bone preserved by prolonged immersion in ethanol, a procedure that yields poor ultrastructural detail. Because microwave irradiation (MWI) facilitates penetra- tion of fixatives, we have investigated whether it can improve preservation by ethanol. Rat tibiae, some labeled with tetracycline, and a human iliac crest biopsy were immersed in
Pharmacoepidemiology and Drug Safety, 2008
Evidence supports bone-specific drugs (BSDs) efficacy in the fracture risk reduction. But treatme... more Evidence supports bone-specific drugs (BSDs) efficacy in the fracture risk reduction. But treatment rates for osteoporosis among high-risk patients are far below the recommended guidelines. A major concern about BSDs is the lack of adherence with treatment. To determine if BSDs decrease fracture risk in high-risk elderly women in real clinical setting. A nested case-control design was used in a cohort of elderly women from the Quebec health databases. Women enter into the cohort if they are 70 years or older between 1995 and 2003. Nested case-controls were designed for women with a diagnosis of osteoporosis (OP) and for those with a prior fracture. All cases of fractures occurring during follow-up were matched with 10 randomly selected controls based on age, time period, bone mass density testing, and having a diagnosis of OP or a prior fracture. Use of BSDs before the index date was categorized as follows: short-term (< or =1 year), intermediate-term (>1 and < or = 3 years), and long-term (>3 years). We used an adjusted conditional logistic regression model to assess BSD effect on fracture. Among 3170 women who had a fracture, of these women, 1824 had OP and 1346 had a prior fracture. Only long-term exposure to BSDs among women with OP reduced the fracture risk by 16% (odds ratio: 0.84; 0.73-0.97). Among women with OP, a high number of medical services or use of anticonvulsants or narcotics increased the fracture risk by 12-73%. Among women with a prior fracture, a high number of medical services or risk of fall or use of benzodiazepines, antidepressants, or narcotics increased the fracture risk by 23-77%. The incidence of fractures decreased by 16% among women with OP when more than 80% of BSDs was used for at least 3 years. Among women with a prior fracture, fracture risk reduction was not significant. Exposure to BSDs among women with a prior fracture is troubling, given that only approximately 12% of these individuals were being treated, and only 2% was using BSDs for the long term.
Pharmacoepidemiology and Drug Safety, 2005
It has been established that women who have had a first osteoporotic fracture are at a significan... more It has been established that women who have had a first osteoporotic fracture are at a significantly greater risk of future fractures. Effective antiresorptive treatments (ART) are available to reduce this risk, yet little information is available on trends in ART drug use among the elderly. The objective is to estimate the rate ratio (RR) of having an ART prescription filled among elderly women and its relation to selected determinants from 1995 through 2001. A cohort design was used. Through random sampling, we selected 40% of the women aged 70 years and older listed in the Régie de l'assurance maladie du Québec (RAMQ) health database. The women were grouped into four cohorts (for 1995, 1996, 1998 and 2000). January 1 was established as the index date within each cohort (1995, 1996, 1998 and 2000). The dependent variable was the RR of having at least one prescription of ART drugs filled during the year following the index date among women with and without prior use. ART users were divided in two groups: bone-specific drugs (bisphosphonates, calcitonin, raloxifen) and HRT (hormone replacement therapy). The independent variable was whether or not (control) there had been an osteoporotic-related fracture. The RR was determined for having at least one prescription of bone-specific drugs or of HRT filled during the year following the index date using a Cox regression adjusted for age, chronic disease score (CDS) and prior bone mineral density (BMD) test. Crude rates of BMD testing (per 500 person-years) ranged from 20.4 (1995) to 41.1 (2000) in women who had had an osteoporotic-related fracture, and from 4.4 to 15.3 in controls. The crude rate of women (per 100 person-years) who had had an osteoporotic-related fracture and who took at least one bone-specific drug during follow-up ranged from 1.9 in 1995 to 31 in 2000 among those with prior osteoporotic-related fracture, and from 0.5 in 1995 to 11 in 2000 for controls; the corresponding figures for HRT ranged 6.7 in 1995 to 13 in 2000, and from 8.4 in 1995 to 11 in 2000 respectively. BMD test is the only major factor affecting the adjusted RR of having a prescription filled for bone-specific drugs (RR of 10.44; 6.91-15.79 in 1995 and RR of 3.68; 3.30-4.10 in 2000) or HRT (RR of 2.08; 1.64-2.64 in 1995 and RR of 1.44; 1.17-1.77 in 2000), particularly among women who had not had prior use. The fact of having a fracture status does significantly affect the RR of having at least one bone-specific drug prescription filled only among women without prior use (RR of 1.71; 1.26-2.33 in 1996 and RR of 1.77; 1.44-2.19 in 2000). The fact of being younger did not affect the RR of having at least one prescription of bone-specific drugs filled, but being younger increased the RR of filling a prescription of HRT. Significant change was seen over time in the number of BMD tests ordered and ART use. Effective osteoporosis interventions are not optimal in the treatment of elderly women in a Canadian health-care system who have had an osteoporotic fracture, given that approximately 25% of women who had had an osteoporotic-related fracture were users of ART.
Journal of Clinical Densitometry, 2009
Micro-computed tomography (micro-CT) is a quantitative 3-dimensional (3D) scanning procedure used... more Micro-computed tomography (micro-CT) is a quantitative 3-dimensional (3D) scanning procedure used to assess trabecular architecture. In the 3-yr oral iBandronate Osteoporosis vertebral fracture trial in North America and Europe (BONE) study, it was found that oral ibandronate administered daily (2.5 mg) or intermittently (20 mg) significantly reduced vertebral fracture risk by 62% ( p 5 0.0001) and 50% ( p 5 0.0006), respectively, vs placebo. Twodimensional histomorphometric analysis of BONE study biopsies indicated that newly formed bone was of normal quality. In the current analysis, micro-CT was used to assess 3D trabecular microarchitecture. Rod and plate distribution was quantified by differential analysis of the triangulated bone surface. Biopsies were obtained from 110 patients, with 84 evaluable by micro-CT. Median structural model index (SMI; a lower SMI indicates an increased ratio of plates to rods and thus, improved trabecular microarchitecture) was 1.001 with ibandronate vs 1.365 with placebo (90% confidence interval [CI] for difference in medians: e0.626, e0.033), and connectivity density was higher in ibandronate-treated patients (median: 3.904 vs 3.112/mm 3 , 90% CI for difference in medians: 0.159, 1.517). This indicates that trabecular microarchitecture was better preserved in patients receiving ibandronate than placebo. Taken together with previous results from BONE, these findings indicate that ibandronate treatment preserves bone strength by maintaining good quality trabecular microarchitecture in women with postmenopausal osteoporosis.
Journal of Clinical Densitometry, 2001
Following a 52-wk randomized controlled trial of intermittent cyclic etidronate therapy in patien... more Following a 52-wk randomized controlled trial of intermittent cyclic etidronate therapy in patients using corticosteroids, we performed a 52-wk open-label trial of calcium alone in 114 corticosteroid-treated patients to determine whether the beneficial effect of etidronate is maintained after the drug is discontinued. All patients were given 500 mg/d of elemental calcium. Sixty-one and 53 patients made up the former placebo and etidronate groups, respectively. A total of 89 (98%) of patients in the former placebo and etidronate groups remained on corticosteroids throughout the second year. The mean (SE) percentage change in bone mineral density of the lumbar spine, femoral neck, and trochanter were compared between groups. The difference between groups in mean percentage change from baseline (wk 0, initiation of etidronate or placebo therapy) in the bone density of the lumbar spine, femoral neck, and trochanter, following 104 wk, was 3.8 (0.9), 3.0 (1.1), and 4.3 (1.1), respectively (p < 0.05, all sites), in favor of the former etidronate group. While not significant, the former placebo group demonstrated a slightly larger rate of decline in bone density over the second year than the former etidronate group at all three sites. Following the discontinuation of etidronate therapy, there was no accelerated bone loss and there was evidence of a residual protective effect in both the lumbar spine and femoral neck for up to 1 yr posttreatment.
Journal of Bone and Mineral Research, 2006
Transiliac bone biopsies were obtained from 55 women treated with teriparatide or placebo for 12-... more Transiliac bone biopsies were obtained from 55 women treated with teriparatide or placebo for 12-24 months. We report direct evidence that modeling bone formation at quiescent surfaces was present only in teriparatide-treated patients and bone formation at remodeling sites was higher with teriparatide than placebo.
Contemporary Clinical Trials, 2008
Recognizing Osteoporosis and its Consequences in Quebec (ROCQ) is an ongoing patient health-manag... more Recognizing Osteoporosis and its Consequences in Quebec (ROCQ) is an ongoing patient health-management programme aimed at evaluating the diagnostic and treatment care gaps for osteoporosis following a fragility fracture, and subsequently initiating and measuring interventions to decrease these gaps in women 50 years of age and over. Hospitals servicing approximately half of the population of the Province of Quebec (Canada) are participating in the ROCQ programme. Women with fragility and traumatic fractures are approached during their visit to a cast or outpatient clinic and are subsequently contacted by telephone 0 to 16 weeks after their fracture (phase 1). During the first phone contact, they are invited to answer a questionnaire aimed at identifying the specific circumstances of their fracture and asked to participate in an observational study that could last up to 18 months. Based on this initial questionnaire, patients are classified as having either experienced a fragility or traumatic fracture. During the first phone contact, there is no reference about the possible association between the fracture and osteoporosis and no investigation or intervention is proposed. Six to eight months after the fracture event (phase 2), women are again contacted by phone to complete a questionnaire that evaluates the diagnostic and treatment rates for osteoporosis. At this phase of the programme, women with fragility fractures are randomized to one of the three following intervention groups: 1) Educational Video Group, 2) Documentation Group and 3) Control Group. Participants are contacted 12 to 14 months after the intervention (phase 3) to evaluate the efficacy of the interventions on the diagnosis and treatment rates of osteoporosis. All participants with fragility or traumatic fractures who consent will be followed for 20 years using data from the Québec Ministry of Health database to measure the association between the index fracture and future fracture risk.
Clinical Biochemistry, 2009
Osteoporosis is the most common cause of fragility fractures. Bone remodelling is essential for r... more Osteoporosis is the most common cause of fragility fractures. Bone remodelling is essential for repairing damaged areas within bone to preserve bone strength and for assisting in mineral homeostases. In young adults, bone remodelling is usually balanced with approximately as much bone replaced as is removed during each remodelling cycle. However, when remodelling becomes accelerated in combination with an imbalance that favours bone resorption over formation, such as during menopause, precipitous losses in bone mass occur. Bone turnover markers (BTMs) measure the rate of bone remodelling allowing for a dynamic assessment of skeletal status and hold promise in identifying those at highest risk of rapid bone loss and subsequent fracture. Further, the use of BTMs to monitor individuals administered osteoporosis therapy is attractive as monitoring anti-fracture efficacy with bone mineral density has significant limitations. This review details remodelling biology, pre-analytical and analytical sources of variability for BTMs, describes the most commonly used resorption and formation markers, and offers some guidelines for their use and interpretation in the laboratory and the clinic.
British Journal of Clinical Pharmacology, 2008
• Compliance with alendronate and risedronate is suboptimal. • Few studies have specifically eval... more • Compliance with alendronate and risedronate is suboptimal. • Few studies have specifically evaluated the impact of noncompliance with alendronate or risedronate on the incidence of osteoporotic fractures in community-dwelling elderly women.
Bone, 2008
Degree of mineralization of bone (DMB) is a major intrinsic determinant of bone strength at the t... more Degree of mineralization of bone (DMB) is a major intrinsic determinant of bone strength at the tissue level but its contribution to the microhardness (Vickers indentation) at the intermediary level of organization of bone tissue, i.e., Bone Structural Units (BSUs), has never been assessed. The purpose of this study was to analyze the relationship between the microhardness, the DMB and the organic matrix, measured in BSUs from human iliac bone biopsies. Iliac bone samples from controls and osteoporotic patients (men and women), embedded in methyl methacrylate, were used. Using a Vickers indenter, microhardness (kg/mm 2 ) was measured, either globally on surfaced blocks or focally on 100 μm-thick sections from bone samples (load of 25 g applied during 10 sec; CV = 5%). The Vickers indenter was more suited than the Knoop indenter for a tissue like bone in which components are diversely oriented. Quantitative microradiography performed on 100 μm-thick sections, allowed measurement of parameters reflecting the DMB (g/cm 3 ). Assessed on the whole bone sample, both microhardness and DMB were significantly lower (−10% and −7%, respectively) in osteoporotic patients versus controls (p b 0.001). When measured separately at the BSU level, there were significant positive correlations between microhardness and DMB in controls (r 2 = 0.36, p b 0.0001) and osteoporotic patients (r 2 = 0.43, p b 0.0001). Mineralization is an important determinant of the microhardness, but did not explain all of its variance. To highlight the role of the organic matrix in bone quality, microhardness of both osteoid and adjacent calcified matrix were measured in iliac samples from subjects with osteomalacia. Microhardness of organic matrix is 3-fold lower than the microhardness of calcified tissue. In human calcanei, microhardness was significantly correlated with DMB (r 2 = 0.33, p = 0.02) and apparent Young's modulus (r 2 = 0.26, p = 0.03). In conclusion, bone microhardness measured by Vickers indentation is an interesting methodology for the evaluation of bone strength and its determinants at the BSU level. Bone microhardness is linked to Young's modulus of bone and is strongly correlated to mineralization, but the organic matrix accounts for about one third of its variance.
Medical education, 2012
Medical Education 2012: 46: 357-365 Context Current debate in medical education focuses on the n... more Medical Education 2012: 46: 357-365 Context Current debate in medical education focuses on the nature of 'competency-based medical education' (CBME) and whether or not it should be adopted. Many medical schools claim to run 'competency-based' curricula, but the structure of their programmes can differ radically. A review of the existing CBME literature reveals that little attention has been paid to defining the concept of competence. A straightforward examination of what is meant by the term 'competence' is noticeably missing from the literature, despite its impact on medical training. Objectives This paper aims to illustrate the varying conceptions of 'competence' by comparing and contrasting definitions provided in the health sciences education literature and discussing their respective impacts on medical education. Methods A systematic review of recent publications in medical education journals published in English and French was conduct...
Uploads
Papers by Louis-georges Ste-marie