Papers by Peter Vestergaard
Bone, 2016
Diabetes mellitus is associated with an increased fracture risk, however the fracture risk is 7 f... more Diabetes mellitus is associated with an increased fracture risk, however the fracture risk is 7 fold increased in patients with type 1 diabetes (T1D) and 1.4 fold increased in patients with type 2 diabetes (T2D) with decreased and increased bone mineral density, respectively. Oral ingestion of glucose causes an acute decrease in bone turnover markers, and thus glucose levels may affect bone turnover in diabetes. The aim was to examine disparities in bone turnover markers between patients with T1D and T2D and evaluate the effect of glucose on bone turnover. A cross-sectional study was conducted. Patients diagnosed with T1D (n=98) or T2D (n=96) were included from the outpatient clinics at two University Hospitals. All individuals had normal renal function. Glucose and bone turnover markers were measured in non-fasting blood samples. P-procollagen type 1 amino terminal propeptide (P1NP), p-osteocalcin (OC), and s-Receptor Activator of Nuclear factor Kappa beta Ligand (RANKL) were lower in patients with T2D compared to T1D, and s-osteoprotegerin (OPG) was higher in T2D. P-C-terminal cross-linked telopeptide of type-I collagen (CTX), p-fibroblast growth factor-23 (FGF-23), p-sclerostin, and p-undercarboxylated osteocalcin (ucOC) were similar in between the two groups of patients. Increasing non-fasting glucose levels were inversely related to p-CTX, p-P1NP, p-OC, and p-ucOC and directly related to s-OPG in simple linear and multiple linear regressions adjusted for factors influencing bone turnover markers including HbA1c. Bone turnover markers were lower in patients with T2D compared to T1D. Acute blood glucose alterations may change bone turnover mediated by OPG and have detrimental effects on bone health in diabetes. ClinicalTrials.govNCT01870557.
The British journal of nutrition, Jan 2, 2015
In a prospective cohort study, the association between maternal vitamin D status during pregnancy... more In a prospective cohort study, the association between maternal vitamin D status during pregnancy and offspring forearm fractures during childhood and adolescence was analysed in 30 132 mother and child pairs recruited to the Danish National Birth Cohort between 1996 and 2002. Data on characteristics, dietary factors and lifestyle factors were collected on several occasions during pregnancy. We analysed the association between predicted vitamin D status, based on a subsample with 25-hydroxyvitamin D (25(OH)D) biomarker measurements (n 1497) from gestation week 25, and first-time forearm fractures among offspring between birth and end of follow-up. Diagnoses were extracted from the Danish National Patient Register. Multivariable Cox regression models using age as the underlying time scale indicated no overall association between predicted vitamin D status (based on smoking, season, dietary and supplementary vitamin D intake, tanning bed use and outdoor physical activity) in pregnancy...
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, Jan 14, 2015
Oral bisphosphonates (BPs) are highly effective in preventing fractures and are recommended first... more Oral bisphosphonates (BPs) are highly effective in preventing fractures and are recommended first-line therapies for patients with osteoporosis. We identified the incidence and predictors of oral BP treatment failure, defined as the incidence of ≥2 fractures while on treatment (≥2 FWOT) among users with high adherence. Fractures were considered after six months from treatment initiation and up to six months after discontinuation. Data from computerized records and pharmacy invoices were obtained from Sistema d'Informació per al Desenvolupament de l'Investigació en Atenció Primària (SIDIAP) (Catalonia, Spain) and Danish Health Registries (Denmark) for all incident users of oral BPs in 2006-2007 and 2000-2001 respectively. Fine and Gray survival models using backward-stepwise selection (p-entry 0.049; p-exit 0.10) and accounting for the competing risk of therapy cessation were used to identify predictors of ≥2 FWOT among patients having persisted with treatment ≥6months with o...
Pharmacoepidemiology and Drug Safety, 2015
Dipeptidyl peptidase-4 inhibitors (DPP4-Is) are a new class of anti-hyperglycemic drugs which mig... more Dipeptidyl peptidase-4 inhibitors (DPP4-Is) are a new class of anti-hyperglycemic drugs which might have a potential beneficial effect on bone metabolism. Data on the effect of DPP4-I use and fracture risk is limited and conflicting. The aim of the present study was to investigate the association between use of DPP4-Is and fracture risk. A case-control study was conducted using data from the Danish National Health Service. Cases were those who sustained a fracture, and controls were those without a fracture during the study period (2007-2011), all aged 18 years and older. Conditional logistic regression estimated the odds ratios of fracture with current use of DPP4-I use. Analyses were adjusted for comorbidities and recent drug use. Among the cases there were 6993 current non-insulin anti-diabetic drug (NIAD) users (excluding incretin users) and 643 DPP4-I users. There were 7209 NIAD users (excluding incretin users) among the controls and 707 DPP4-I users. Current DPP4-I use was not associated with risk of any fracture (adjusted [adj.] OR: 0.97, 95% CI: 0.79-1.18) or major osteoporotic fracture (adj. OR: 0.96, 95% CI: 0.72-1.28). Stratification of current DPP4-I use to cumulative and average daily dose did not show an association. In a population-based case-control study we identified that short-term use of DPP4-I was not associated with fracture risk as compared to users of other anti-hyperglycemic drugs. Additionally, results suggest that increasing daily dose and cumulative DPP4-I exposure were not associated with fracture risk. However, more research is needed to assess the effect of long-term DPP4-I use on the risk of fracture. Copyright © 2015 John Wiley & Sons, Ltd.
Calcified Tissue International, 2015
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a new class of drugs that might have a ... more Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a new class of drugs that might have a potential beneficial effect on bone metabolism. Data on the effect of GLP-1 RAs and fracture risk are lacking. The aim of the present study was to investigate the association between the use of GLP-1 and the risk of fracture. A case-control study was performed using Danish National Health Service data. Cases were those who sustained a fracture and controls were those without a fracture during the study period (2007-2011), all aged 18 years and above. Conditional logistic regression estimated the odds ratios (OR) of fracture with current use of DPP4-I use. Analyses were adjusted for comorbidities and recent drug use. Among cases (n = 229,114), there were 6993 current non-insulin anti-diabetic drug (NIAD) users (excluding incretin users) and 255 GLP-1 RA users. Similarly, among controls (n = 229,114), 7209 were NIAD users (excluding incretin users) and 220 were GLP-1 RA users. Current GLP-1 RA use was not associated with a decreased risk of fracture [adjusted (adj.) OR 1.16; 95 % CI 0.83-1.63]. Osteoporotic fracture risk was also not associated with current GLP-1 RA use (adj. OR 0.78; 95 % CI 0.44-1.39). In our nation-wide case-control study, we identified that the use of GLP-1 RA was not associated with fracture risk as compared to the use of other anti-hyperglycemic drugs. Additionally, current GLP-1 RA use, stratified by cumulative or average daily dose, is not associated with fracture risk. Further research should focus on long-term use of GLP-1 RA and fracture risk.
Frontiers in Endocrinology, 2015
Type-1 and type-2 diabetes mellitus (DM) are associated with an increased fracture risk and possi... more Type-1 and type-2 diabetes mellitus (DM) are associated with an increased fracture risk and possibly an increased risk of death following a fracture. To investigate the association between diabetes-related drugs and mortality following a fracture. A nested case-control study was conducted. Cases were patients with DM who died following a fracture; controls were DM patients not dying after a fracture. We identified DM patients using the Danish National Hospital Discharge Register (1977-2011) and included information on date of DM diagnosis, date of fracture, and comorbidities. From the Danish Cause of Death Register, the date of death was collected (2008-2011). From the Central Region of Jutland, Denmark, medication use was collected (2008-2011). Analysis was performed by unconditional logistic regression. Two thousand six hundred twenty one diabetes patients with a fracture following the diabetes diagnosis and with information on medication use were included. Of these, 229 died. In a multivariate analysis, statin use [n = 1,106 (42%) statin users, odds ratio (OR) = 0.60, 95% confidence interval, p = 0.012] decreased the risk of dying subsequent to a fracture. Male gender (OR = 1.57, p = 0.005), increasing age (OR = 1.08, p < 0.001), a diagnosis of retinopathy (OR = 2.12, p = 0.008), heart failure (OR = 1.68, p = 0.004), and use of glucocorticoids (OR = 2.22, p = 0.001) were associated with an increased risk of death. None of the antidiabetics: biguanides, glucagon-like receptor agonists, β-cell stimulants, glitazones, and insulin were associated with mortality. Co-morbidity reflected by late onset complications, heart failure, and glucocorticoid use was associated with an increased risk of mortality subsequent to a fracture. Statin use may reduce mortality subsequent to a fracture in diabetes patients. Clinical trials are needed to determine whether diabetes patients with a fracture should initiate statin treatment.
Nutrients, 2015
Limited evidence exists for an association between maternal diet during pregnancy and offspring b... more Limited evidence exists for an association between maternal diet during pregnancy and offspring bone health. In a prospective study, we examined the association between dietary patterns in mid-pregnancy and offspring forearm fractures. In total, 101,042 pregnancies were recruited to the Danish National Birth Cohort (DNBC) during 1996-2002. Maternal diet was collected by a food frequency questionnaire. Associations were analyzed between seven dietary patterns extracted by principal component analysis and offspring first occurrence of any forearm fracture diagnosis, extracted from the Danish National Patient Register, between time of birth and end of follow-up (<16 year) (n = 53,922). In multivariable Cox regression models, offspring of mothers in the fourth vs. first quintile of the Western pattern had a significant increased risk (Hazard ratio, 95% confidence interval: 1.11, 1.01-1.23) of fractures, and there was a borderline significant positive trend (p = 0.06). The other dieta...
Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, 2011
Treatment of benign prostate hyperplasia with α-blockers may affect blood pressure while treatmen... more Treatment of benign prostate hyperplasia with α-blockers may affect blood pressure while treatment with 5-α-reductase inhibitors may affect conversion of testosterone potentially leading to osteoporosis. In our study, neither 5-α-reductase inhibitors nor α-blockers were associated with negative effects on fractures, α-blockers perhaps being associated with a limited decrease in fractures. The objective is to study fracture risk associated with drugs for benign prostate hyperplasia. The hypotheses were that (1) α-blockers may elevate fracture risk by causing presyncope/falls and (2) 5-α-reductase inhibitors may elevate fracture risk by lowering dihydrotestosterone. This is a nationwide case-control study using all 9,719 male fracture patients aged ≥60 years in the year 2000 as cases and drawing 29,156 age- and gender-matched controls. The main exposure was the use of the drugs mentioned above for benign prostate hyperplasia. Confounder control included social variables, contacts to h...
Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, 2010
Prior studies have associated raloxifene and strontium ranelate with deep venous thromboembolism ... more Prior studies have associated raloxifene and strontium ranelate with deep venous thromboembolism and pulmonary embolism. In a cohort study, we observed an increased risk also with the bisphosphonates. However, the increase was present already before the start of bisphosphonates pointing at an effect of the underlying condition. We seek to study the association between use of drugs against osteoporosis and risk of deep venous thromboembolism (DVT) and pulmonary embolism (PE). Nationwide register-based cohort study from Denmark with all users of bisphosphonates and other drugs against osteoporosis between 1996 and 2006 (n = 103,562) as cases and three age- and gender-matched controls from the general population (n = 310,683). Before start of a drug against osteoporosis, an increased risk of DVT/PE was present in the crude analysis for alendronate, etidronate, and risedronate. However, upon adjustment, this increase in risk disappeared. Before start of raloxifene, a decreased risk of D...
European journal of endocrinology / European Federation of Endocrine Societies, Jan 2, 2015
Context: Impairments of muscle function and strength in patients with primary hyperparathyroidism... more Context: Impairments of muscle function and strength in patients with primary hyperparathyroidism (PHPT) are rarely addressed although decreased muscle function may contribute to increased fracture risk. Objective: We aimed to assess changes in muscle strength, muscle function, postural stability, quality of life (QoL), and well-being during treatment with vitamin D or placebo before and after parathyroidectomy (PTX) in PHPT patients. Design: Randomized placebo controlled trial. Patients: We included 46 PHPT patients, mean age 58 (range 29-77) years and 35 (76%) were women. Interventions: Daily treatment with 70 microgram (2,800 IU) cholecalciferol or placebo for 52 weeks. Treatment was administered 26 weeks prior to PTX and continued for 26 weeks after PTX. Main outcome measures: Changes in QoL and measures of muscle strength and function. Results: Preoperatively, 25-hydroxyvitamin D (25OHD) increased significantly (50 to 94 nmol/L) compared with placebo (57 to 52 nmol/L). We did n...
Clinical evidence, 2005
The lifetime risk of fracture in white women is 20% for the spine, 15% for the wrist, and 18% for... more The lifetime risk of fracture in white women is 20% for the spine, 15% for the wrist, and 18% for the hip, with an exponential increase in risk beyond the age of 50 years. We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of bisphosphonates to prevent fractures in postmenopausal women? What are the effects of pharmacological treatments other than bisphosphonates to prevent fractures in postmenopausal women? What are the effects of non-pharmacological treatments to prevent fractures in postmenopausal women? We searched: Medline, Embase, The Cochrane Library, and other important databases up to September 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). We found 71 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. In this systematic review we present information relating to the effectiveness and safety of the following interventions: alendronate, calcitonin, calcium, calcium plus vitamin D, clodronate, denosumab, etidronate, exercise, hip protectors, hormone replacement therapy, ibandronate, multifactorial non-pharmacological interventions, pamidronate, parathyroid hormone, raloxifene, risedronate, strontium ranelate, vitamin D, vitamin D analogues, and zoledronate.
International Journal of Cardiology, 2015
Type 2 diabetes (DM) increases the risk of cardiovascular disease. We investigated the effects of... more Type 2 diabetes (DM) increases the risk of cardiovascular disease. We investigated the effects of antidiabetic drugs on the composite endpoint (CE) of ischemic heart disease, heart failure or stroke in DM patients. We conducted a nested case-control study. Cases were DM patients who subsequently suffered from CE; controls were DM patients with no history of CE after DM diagnosis. Using the Danish National Hospital Discharge Register, we included DM patients with information on date of DM diagnosis, date of CE, and comorbidities. From the Central Region of Jutland, Denmark, medication use and biochemical parameters were collected. Logistic regression analyses were conducted and mutually adjusted for comorbidities, pharmaceutical use, and biochemical parameters. 10,073 DM patients were included (65,550person-years). 1947 suffered from a subsequent CE. CE prior to DM diagnosis (OR=20.18, 95% CI: 16.88-24.12), neuropathy (OR=1.39, 95% CI: 1.05-1.85) and peripheral artery disease (OR=1.31, 95% CI: 1.02-1.69) increased the risk of CE. Biguanides (OR=0.62 95% CI; 0.54-0.71) and liraglutide (OR=0.48 95% CI; 0.38-0.62) significantly decreased the risk of CE as did statin treatment (OR=0.63, 95% CI: 0.54-0.72). DPP-4 inhibitors, insulin and β-cell stimulating agents had neutral effect. When results were adjusted for biochemical risk markers (1103 patients, 7271person-years, 189 cases), biguanides (OR=0.54, 95% CI: 0.34-0.87) and liraglutide (OR=0.32, 95% CI: 0.14-0.70) treatment retained a significant risk reduction. The effect of liraglutide was dose and duration dependent (p&amp;amp;amp;amp;amp;amp;lt;0.05). We have shown an association between the use of biguanides and liraglutide and a reduced risk of CE in DM patients.
PLoS ONE, 2014
Background: Studies investigating the association between maternal vitamin D status and offspring... more Background: Studies investigating the association between maternal vitamin D status and offspring bone mass measured by dual-energy X-ray absorptiometry (DXA) during childhood have shown conflicting results. Purpose: We used occurrence of bone fractures up to the age of 18 as a measure reflecting offspring bone mass and related that to maternal vitamin D status. Methods: The Danish Fetal Origins 1988 Cohort recruited 965 pregnant women during 1988-89 at their 30 th gestation week antenatal midwife visit. A blood sample was drawn and serum was stored, which later was analyzed for the concentration of 25-hydroxyvitamin D (25(OH)D) by the liquid chromatography coupled with a tandem mass spectrometric method (LC-MS/MS). Outcome was diagnosis of first time bone fractures extracted from the Danish National Patient Register. Results: Vitamin D status was available for 850 women. The median (5 th -95 th percentile) 25(OH)D was 76.2 (23.0-152.
PLoS ONE, 2011
Background: Extended physical inactivity causes disuse osteoporosis in humans. In contrast, brown... more Background: Extended physical inactivity causes disuse osteoporosis in humans. In contrast, brown bears (Ursus arctos) are highly immobilised for half of the year during hibernation without signs of bone loss and therefore may serve as a model for prevention of osteoporosis.
Osteoporosis International, 2004
Based on animal studies, statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) hav... more Based on animal studies, statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) have been suggested as potential agents in the treatment of osteoporosis. In some epidemiological studies, statins have been associated with a reduced fracture risk. Our objective was to examine associations between statin treatment and risk of hip fracture in a population-based case-control study. A total of 6660 subjects with hip fracture and 33,274 gender- and age-matched population controls were identified from 1 January 1994 to 31 December 2001 using the Hospital Patient Register in North Jutland County, Denmark, and the Danish Central Personal Registry, respectively. Data on redeemed prescriptions for statins within the last 5 years before the index date were retrieved from a population-based prescription database. We used conditional logistic regression to estimate odds ratios (OR) for hip fracture according to use of statin prescriptions adjusted for potential confounding factors, i.e. gender, other diseases, and use of other drugs known to affect bone metabolism and fracture risk. After adjustment for potential confounders, statin treatment was associated with a reduced risk of hip fracture (OR=0.68; 95% confidence interval: 0.50-0.93) for those who had redeemed more than three prescriptions for a statin drug. We found that risk of hip fracture decreased with the number of statin prescriptions. Stratified analyses on gender and age did not reveal any major differences between men and women or among different age groups on the estimates between use of statins and hip fracture risk. Our findings support an association between statin treatment and a reduced hip fracture risk. However, it is unclear whether this association is causal.
Osteoporosis International, 2011
Prior studies have suggested an association between bisphosphonate use and subtrochanteric fractu... more Prior studies have suggested an association between bisphosphonate use and subtrochanteric fractures. This cohort study showed an increased risk of subtrochanteric and femoral shaft fractures both before and after the start of drugs against osteoporosis including bisphosphonates. This may suggest an effect of the underlying disease rather than the drugs used. The objective of this study is to determine the association between drugs against osteoporosis and the risk of femoral shaft and subtrochanteric fractures. No separation was made between atypical and typical fractures. Nationwide cohort study from Denmark with all users of bisphosphonates and other drugs against osteoporosis between 1996 and 2006 (n = 103,562) as exposed group and three age- and gender-matched controls from the general population (n = 310,683). Adjustments were made for prior fracture, use of systemic hormone therapy, and use of systemic corticosteroids. After initiation of therapy, an increased risk of subtrochanteric fractures was seen for alendronate (hazard ratio (HR) = 2.41, 95% confidence interval (CI) 1.78-3.27), etidronate (HR = 1.96, 95% CI 1.62-2.36), and clodronate (HR = 20.0, 95% CI 1.94-205), but not for raloxifene (HR = 1.06, 95% CI 0.34-3.32). However, an increased risk of subtrochanteric fractures was also present before the start of alendronate (OR = 2.36, 95% CI 2.05-2.72), etidronate (OR = 3.05, 95% CI 2.59-3.58), clodronate (OR = 10.8, 95% CI 1.14-103), raloxifene (OR = 1.90, 95% CI 1.07-3.40), and strontium ranelate (OR = 2.97, 95% CI 1.07-8.27). Similar trends were seen for femoral shaft fractures and overall fracture risk. After the start of etidronate, no dose-response relationship was present (p for trend, 0.54). For alendronate, a decreasing risk was present with increasing average daily dose (p for trend, &lt;0.01). Although an increased risk of femoral shaft and subtrochanteric fractures are seen with the use of several types of bisphosphonates, the increased risk before the start of the drugs may point at an effect of the underlying disease being treated. The increased risk may, thus, perhaps be due to confounding by indication.
Osteoporosis International, 2011
Prior studies have associated fatal stroke with raloxifene. In a cohort study, we found no excess... more Prior studies have associated fatal stroke with raloxifene. In a cohort study, we found no excess risk of stroke with raloxifene; whereas, an excess risk of stroke and fatal stroke was seen with alendronate and etidronate. However, the excess risks were small.
Osteoporosis International, 2005
To compare the number of patients diagnosed with osteoporosis and osteoporotic fractures in Denma... more To compare the number of patients diagnosed with osteoporosis and osteoporotic fractures in Denmark, with the number of subjects expected to have osteoporosis. From the National Hospital Discharge Register, records for all patients diagnosed with osteoporosis and/or with osteoporotic fractures between 1995 and 1999 were retrieved. Based on normal Danish values for BMD, the expected number of subjects aged 50 years or more with osteoporosis according to the WHO definition was calculated. The estimated prevalence of osteoporosis was 40.8% of women aged &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;or=50 years and 17.7% among men. The expected annual incidence was 58,658/million inhabitants in women &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;or=50 years of age and 23,648/million in men &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;or=50 years. However, the observed incidence was only 4,823 and 862/million per year, respectively (8.2% and 3.6% of the expected). In 1999, a total of 34,691 hip, spine, and forearm fractures were reported in subjects &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;or=50 years, and of these, 18,566 were potentially attributable to osteoporosis (14,240 fractures in women and 4,326 in men equaling 14,976 and 5,297/million per year). Only 0.3% of men &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;or=50 years were receiving a bisphosphonate, while 2.2% of women received a bisphosphonate or raloxifene. Among women &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;or=50 years, 27.7% received hormone replacement therapy. Osteoporotic fractures of the hip, spine, and forearm are rather frequent in Denmark, but the diagnosis of osteoporosis is rarely used. It seems that osteoporosis is markedly underdiagnosed and undertreated in Denmark as probably also elsewhere. This may have significant implications for the prevention of osteoporotic fractures.
Osteoporosis International, 2006
Orthopaedic Nursing, 2003
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Papers by Peter Vestergaard