Biomedical subjects

L Rejnmark

Publications and source records attributed to L Rejnmark.

14 recordsLinked to original sources

PubMed2003

Dose-effect relations of loop- and thiazide-diuretics on calcium homeostasis: a randomized, double-blinded Latin-square multiple cross-over study in postmenopausal osteopenic women.

BACKGROUND: Thiazide diuretics (TDs) reduce whereas loop diuretics (LDs) increase urinary calcium. We studied the effects of different doses of a TD and LD on electrolytes, calcitropic hormones and biochemical bone markers. SUBJECTS AND METHODS: In a five-period crossover study, comparing four active doses with placebo, 40 postmenopausal women with osteopenia were treated with different doses of LD bumetanide (n = 20, 0.5-2.0 mg per day) or TD bendroflumethiazide (n = 20, 2.5-10 mg per day). Each treatment period lasted 1 week. RESULTS: Urinary calcium decreased dose-dependently in response to the bendroflumethiazide. The best hypocalciuric effect was achieved by 5 mg day-1 of bendroflumethiazide. Total plasma calcium levels increased, whereas ionised calcium at ambient pH-values decreased because of increased pH-values in response to the bendroflumethiazide. Plasma PTH levels did not change, whereas a slight dose-dependent increase occurred in plasma 1,25(OH)2D levels. As a marker of bone formation, plasma osteocalcin levels increased. Conversely, bumetanide dose-dependently increased renal calcium losses with a concomitant increase in plasma PTH and 1,25(OH)2D levels. Plasma osteocalcin levels increased and bone-specific alkaline phosphatase levels decreased dose-dependently. CONCLUSION: Whether a LD or TD is chosen as diuretic therapy affects calcium homeostasis. The effects of LDs are potentially harmful to bone. Further studies are needed to evaluate whether long-term treatment with LDs causes osteoporosis. Until then, we suggest using, if possible, a TD rather than a LD as diuretic therapy in order not to risk deleterious effects on bone metabolism.

Alkaline Phosphatase↗

PubMed2002

Statins decrease bone turnover in postmenopausal women: a cross-sectional study.

BACKGROUND: Statins have been suggested as potential agents in the management of osteoporosis. Reviews of medical records have shown an increased bone mass and some studies have shown a reduced occurrence of fractures in subjects on long-term treatment with statins. We studied the effects of treatment with statins on calcium homeostasis, bone turnover and bone mineral density. DESIGN: In a cross-sectional design, plasma levels of parathyroid hormone (PTH) and biochemical markers of bone turnover, bone mineral density (BMD) and body composition (fat- and lean tissue-mass) were measured in 140 postmenopausal women who had been treated with a statin for more than 2 years (median 4 years) and compared to 140 age- and gender-matched, population-based controls. RESULTS: Plasma levels of bone turnover markers were lower in the statin-treated subjects than in the controls: osteocalcin (-9%, P = 0.03), bone-specific alkaline phosphatase (-14%, P < 0.01), and C-terminal telopeptide of type I collagen (-11%, P < 0.01). On the other hand, plasma PTH levels were 16% higher in the statin-treated subjects than in the controls (P < 0.01). However, body composition and BMD at the lumbar spine, hip, forearm and whole body did not differ between the two groups. No correlation could be demonstrated between changes in biochemical quantities and dose or duration of statin use. CONCLUSION: Our data show that statins affect the function of bone cells. Most likely, the effect is antiresorptive.

Aged↗

PubMed2002

Soluble CD163: a marker molecule for monocyte/macrophage activity in disease.

By immunoprecipitation we have identified a soluble plasma form of CD163 (sCD163), the IL-6 inducible macrophage-receptor for clearing haptoglobin-haemoglobin complexes. A sandwich ELISA for measuring sCD163 was established and used to determine the sCD163 levels in normal subjects and patients with inflammatory and myeloproliferative diseases. In normal subjects, the concentration of sCD163 was high (median 1.9 mg/l) with low intra-individual variation. Highly increased levels were seen in patients with sepsis, myeloid leukaemia and in patients with Gaucher disease characterized by accumulation of tissue macrophages. Although the physiological role of sCD163 remains unknown, our present data suggest that sCD163 might prove to be a valuable marker molecule in infectious and myeloproliferative diseases.

Antigens, CD↗

PubMed2001

Loop diuretics alter the diurnal rhythm of endogenous parathyroid hormone secretion. A randomized-controlled study on the effects of loop- and thiazide-diuretics on the diurnal rhythms of calcitropic hormones and biochemical bone markers in postmenopausal women.

BACKGROUND: Thiazide diuretics (TD) reduce urinary calcium, bone loss and fracture risk. Loop diuretics (LD) may have opposite effects. These effects could depend on induced rhythmic changes in bone and calcium homeostasis. DESIGN: After a run-in period of 7 days, we studied (in a factorial design) the diurnal rhythms of plasma levels of calcium, phosphate, parathyroid hormone (PTH), 1,25-dihydroxyvitamin D and osteocalcin, as well as renal excretions rates of calcium, phosphate, and cross-linked N-terminal telopeptide of type 1 collagen (NTx) in 50 postmenopausal women randomized to treatment with either a thiazide diuretic (TD; bendroflumethiazide, n = 14), a loop diuretic (LD; bumetanide, n = 13), LD plus TD (bendroflumethiazide plus bumetanide, n = 11), or placebo (n = 12). RESULTS: In all four groups, all measured quantities showed a diurnal variation. LD caused a steep increase, with a subsequent decrease, in urinary calcium and plasma PTH. The mean 24 h plasma PTH concentration was increased (8.5 +/- 0.9 mmol L-1) compared with placebo (4.4 +/- 0.4 mmol L-1), whereas net 24 h renal calcium excretion did not differ from that of the placebo group due to a rebound hypocalciuria. Compared with placebo, diurnal rhythms of plasma phosphate and osteocalcin were changed with an increase during daytime and a decrease during the night. TD did not alter the diurnal rhythm of any of the measured quantities. However, the 24-h renal calcium excretion decreased, whereas the mean 24-h plasma calcium concentration increased without PTH suppression. LD plus TD caused changes similar to those observed with LD alone. CONCLUSION: One daily dose of LD increases parathyroid activity with alterations in the diurnal pattern of osteocalcin. This could indicate a potential anabolic effect of LD.

Aged↗

PubMed2001

Effects of thiazide- and loop-diuretics, alone or in combination, on calcitropic hormones and biochemical bone markers: a randomized controlled study.

OBJECTIVE: Diuretics are commonly used drugs that in addition to their effect on the cardiovascular system also affect calcium homeostasis and bone metabolism. We evaluated the effects of loop diuretics (LD) and thiazide diuretics (TD) on calcitropic hormones and biochemical bone markers. DESIGN: A total of 50 postmenopausal women were randomized to 7 days of treatment with either the TD bendroflumethiazide, the LD bumetanide, bendroflumethiazide plus bumetanide, or placebo. Blood and urine (24 h) were sampled on each day. Statistical inferences were made versus the concomitant changes in the placebo group. RESULTS: Bendroflumethiazide increased the tubular reabsorption of calcium (TRCa) (+0.46 +/- 0.11%, P=0.009), plasma levels of parathyroid hormones (PTH) (+24 +/- 10%, P=0.06), and 1,25(OH)2D (+12 +/- 6%, P=0.03). Bumetanide decreased the TRCa (-0.5 +/- 0.1%, P=0.01) and increased plasma PTH and 1,25(OH)2D levels (+27 +/- 9%, P=0.02 and +36 +/- 12%, P=0.006, respectively). Treatment with either of the drugs did not alter plasma calcium, osteocalcin, bone alkaline phosphatase (bone-ALP) or urinary NTx/creatinine ratio. However, treatment with both drugs caused an increased plasma calcium level (+2.7 +/- 1.0%, P=0.007) and decreased plasma levels of bone-ALP (-21 +/- 3%, P=0.001), osteocalcin (-6 +/- 3%, P=0.03), and urinary NTx/creatinine ratio (-39 +/- 6%, P=0.001). CONCLUSION: Calcium homeostasis and bone metabolism are to a major degree influenced by diuretic treatment. Surprisingly, LD and TD exerted a similar effect on calcitropic hormones despite their opposite effects on the renal calcium excretion. In clinical practice, treatment with diuretics has to be considered as a cause of parathyroid stimulation.

Aged↗

PubMed2001

Hip fracture prevention: cost-effective strategies.

The available literature on cost benefit, cost effectiveness and cost utility of different drug and non-drug regimens in preventing hip fractures was reviewed. The cost of a hip fracture and of the different treatment regimens varied considerably from one country to another. In primary prevention, potential savings only exceeded costs in women over the age of 70 years treated with hormonal replacement therapy (HRT). In the case of HRT, treating those with low bone mineral density levels (secondary prevention) seems to be more cost effective than general treatment (primary prevention). There are few studies that have compared several different preventive regimens. Cost effectiveness is directly related to the cost of the regimen used because there is no significant difference in their effectiveness. That is, a high cost regimen such as bisphosphonates would be less cost effective than a low cost regimen such as HRT, judged from existing literature. High risk groups can be identified (nursing home residents) and treated with low cost interventions (calcium plus vitamin D or hip protectors). Considerable differences in the estimates used for the efficacy of different regimens in studies exist. Further studies comparing several hip fracture preventive regimens are required in order to establish the most cost-effective strategy.

Adult↗

PubMed2001

Fracture risk in patients with muscular dystrophy and spinal muscular atrophy.

We aimed at studying fracture risk in patients with Duchenne's muscular dystrophy (DMD), Becker's muscular dystrophy (BEMD), and spinal muscular atrophy type II and III (SMA II and III). A self-administered questionnaire was mailed to 293 patients with DMD, BEMD, SMA II or SMA III of which 229 returned the questionnaire. Each respondent was compared with an age- and gender-matched control subject. The mean age was 23.9 +/- 15.9 years for the patients and 23.3 +/- 16.5 years for the controls. There were significantly more fractures among patients than controls after the diagnosis was made (RR = 1.9), but not before. The patients had more fractures of the femurs, lower legs, and upper arms than the controls. Low energy fractures were more frequent in patients than controls (9% vs 0%). Many fractures in the femurs (40%), lower legs (35%), and feet and toes (44%) led to a permanent loss of function. Loss of ambulation was the major risk factor for fractures. In conclusion, fracture risk is increased in neuromuscular disease.

Adolescent↗

PubMed2000

Fractures in patients with primary idiopathic hypothyroidism.

AIM: To study fracture risk and risk factors for fractures in patients with primary idiopathic hypothyroidism (ICD 10: E03.9). DESIGN: Historical follow-up. MATERIAL AND METHODS: A self-administered questionnaire was issued to 628 patients with primary idiopathic levothyroxine-substituted hypothyroidism. A total of 412 (65.6%) responded and of these, 408 could be analyzed. The 408 respondents were age- (+/- 5 years) and gender-matched with 408 normal controls randomly selected from the background population who responded to the same questionnaire. RESULTS: Overall fracture risk was increased in patients compared to controls (relative risk: RR = 1.6, 95% CI: 1.0-2.5). However, the increase was temporary and limited to the period within the first 2 years after the diagnosis of hypothyroidism (RR = 3.1, 95% CI: 1.4-7.0). Before the diagnosis and more than 2 years after the diagnosis, the fracture risk in patients did not deviate from that of the controls. The increase in fracture risk was only significant in the age group above 50 years (RR = 1.8, 95% CI: 1-3.2), and was limited to the forearms (RR = 3.0, 95% CI: 1.4-6.3 for the entire patient population). CONCLUSIONS: There was a temporary increase in fracture risk within the first 2 years after diagnosis of primary idiopathic hypothyroidism. The fracture risk was mainly increased in the age group above 50 years, and the increased risk was limited to the forearms.

Adult↗

PubMed2000

Fracture risk in patients treated for hyperthyroidism.

AIM: To study fracture risk and risk factors for fractures in patients with hyperthyroidism. DESIGN: Historical follow-up. MATERIAL AND METHODS: A total of 864 patients with diffuse toxic goiter (ICD 10: E05.0) or toxic nodular goiter (E05.2) were contacted through a self-administered questionnaire. Each respondent was compared to an age: (+/- 5 years) and gender-matched control from a random sample of the background population who responded to the same questionnaire. RESULTS: Among the patients 621 (72%) responded and of these 617 could be analyzed. Within the first 5 years before the diagnosis, the patients had the same fracture risk as the controls (RR = 1.2, 95% CI; 0.7-2.0). After the diagnosis, fracture risk was elevated among the patients (RR = 1.7, 95% CI: 1.2-2.3), especially in the age group 50 years or older (RR = 2.2, 95% CI: 1.5-3.3). Fracture risk was elevated for fractures of the spine (RR = 8.9, 95% CI: 1.6-48.4), and the forearms (RR = 3.1, 95% CI: 1.6-6.2), but not at other skeletal sites. Treatment with radioactive iodine alone was associated with an increased fracture risk (OR = 2.7, 95% CI: 1.2-6.0), a risk that was not present in patients who, in addition to radioactive iodine, also had received methimazole (RR = 1.5, 95% CI: 0.7-3.2). CONCLUSIONS: Our study demonstrated an increased fracture risk in hyperthyroidism, a fracture risk that was present with radioactive iodine treatment alone, but not in subjects that had received both radioactive iodine and methimazole or other types of antithyroid therapy.

Adult↗

PubMed2000

Fracture risk is increased in Crohn's disease, but not in ulcerative colitis.

AIMS: To study fracture rates and risk factors for fractures in patients with Crohn's disease and ulcerative colitis. METHODS: 998 self administered questionnaires were issued to members of the Danish Colitis/Crohn Association, and 1000 questionnaires were issued to randomly selected control subjects. 845 patients (84.5%) and 645 controls (65.4%) returned the questionnaire (p<0.01). 817 patients and 635 controls could be analysed. RESULTS: Analysis was performed on 383 patients with Crohn's disease (median age 39, range 8-82 years; median age at diagnosis 26, range 1-75 years), 434 patients with ulcerative colitis (median age 39, range 11-86 years; median age at diagnosis 29, range 10-78 years), and 635 controls (median age 43, range 19-93 years, p<0.01). The fracture risk was increased in female patients with Crohn's disease (relative risk (RR) = 2.5, 95% confidence interval (CI) 1.7-3.6), but not in male patients with Crohn's disease (RR = 0.6, 95% CI 0.3-1.3) or in patients with ulcerative colitis (RR = 1.1, 95% CI 0.8-1.6). An increased proportion of low energy fractures was observed in patients with Crohn's disease (15.7% versus 1.4 % in controls, 2p<0. 01), but not in patients with ulcerative colitis (5.4%, 2p=0.30). The increased fracture frequency in Crohn's disease was present for fractures of the spine, feet, and toes and fractures of the ribs and pelvis. Fracture risk increased with increasing duration of systemic corticosteroid use in Crohn's disease (2p=0.028), but not in ulcerative colitis (2p=0.50). CONCLUSIONS: An increased risk of low energy fractures was observed in female patients with Crohn's disease, but not in male patients with Crohn's disease or in patients with ulcerative colitis.

Adolescent↗

PubMed1999

Fracture risk is increased in epilepsy.

OBJECTIVES: To study fracture rates and risk factors for fractures in non-institutionalized patients with epilepsy. MATERIAL AND METHODS: Historical follow-up. Self-administered questionnaires were issued to 755 patients with epilepsy (ICD 10: G40.0 to G40.9) and 1000 randomly selected controls from the background population. RESULTS: A total of 345 patients (median age: 45, range 17-80 years) and 654 control subjects (median age: 43, range 19-93 years) returned the questionnaire. Before epilepsy was diagnosed there was no difference in overall fracture rate between patients and controls (RR = 1.0, 95% CI: 0.8-1.3). After the diagnosis the overall fracture rate was significantly higher in the patients (RR = 2.0, 95% CI: 1.6-2.5). Fractures of the spine, forearms, femurs, lower legs, and feet and toes were significantly increased. Fractures related to seizures accounted for 33.9% (95% CI: 25.3-43.5%) of all fractures. After elimination of seizure related fractures the increase in fracture frequency was only borderline significant: RR = 1.3 (95% CI: 1.0-1.7, P = 0.042). No difference in fracture energy between patients and controls was observed (low energy fractures: 1.7/1.4%, medium energy fractures: 59.8/52.0%, and high energy fractures: 38.3/46.6%). Use of phenytoin (OR = 2.4, 95% CI: 1.1-5.4) and a family fracture history (OR = 2.4, 95% CI: 1.3-4.6) was associated with an increased fracture risk. CONCLUSIONS: Fractures were more common in epileptics than in controls especially among users of phenytoin. Most of the increase in fracture frequency was related to seizures and not to low bone biomechanical competence.

Adolescent↗

PubMed1998

Fracture rates and risk factors for fractures in patients with spinal cord injury.

AIM: To study fracture rates and risk factors for fractures in patients with spinal cord injuries. MATERIAL AND METHODS: A self-administered questionnaire was mailed to 646 members of the Danish Paraplegic Association and 1000 randomly selected normal controls. 438 patients (309 males, 129 females, 67.8%) and 654 controls (332 males, 322 females, 65.4%) returned the questionnaire. Median age in patients was 42, range 10-80 years, and in controls 43, range 19-93 years (2p = 0.25). RESULTS: The crude fracture rate was 2% per year in patients and 1% per year in controls (RR = 2.0, P < 0.001). Low-energy fractures were much more prominent in patients (19.0% of all fractures) than in controls (1.4%, P < 0.001). The fracture rate did not differ before the injury but increased after the injury to a constant level from the third year and forward. Fractures of the lower extremities were more prominent in patients than controls (femurs: RR = 23.4, P < 0.001, lower legs: RR = 5.2, P < 0.001, feet/toes: RR = 2.4, P = 0.006) while fractures of the forearms (P < 0.001) and clavicles (P = 0.03) were absent among patients. Fractures were more frequent in female patients (RR = 1.6, P = 0.008) and in male patients with a family history of fractures (RR = 2.0, P = 0.004). CONCLUSIONS: Low-energy fractures especially of the lower extremities are frequent in spinal cord injury patients and especially among female patients. The forearms seem protected from fractures.

Adolescent↗

PubMed1998

[Diuretics and osteoporosis].

Thiazide diuretics lower while loop diuretics promote calcium excretion by the kidney. Several studies have found thiazide use to be associated with higher bone mineral density and some have found that thiazides reduce the risk of hip fracture. The mechanisms by which thiazides favour preservation of the bones are uncertain. Thiazide use results in decreased renal calcium excretion and thiazide users have been shown to have lower levels of S-PTH and S-1,25-dihydroxy-vitamin D. The beneficial bone effects may result from a decrease in PTH-stimulated bone resorption and an associated reduction in the bone turn-over rate. Whether loop diuretics increases the bone turn-over by augmenting the urinary calcium excretion is more controversial as only few studies have been carried out on loop diuretics. However, in these studies the use of loop diuretics have been associated with decreased bone mineral density and increased risk of fractures. Future research should determine the minimal dose of thiazide therapy necessary to produce a sustained hypocalciuric effect and in addition the influence of diuretic dose on bone turn-over. Equally important is the need to evaluate potential unwanted effects of loop diuretics. In the mean time, thiazide diuretics may be used safely while some caution is necessary in the long term use of loop diuretics in patients who are prone to osteoporosis.

Aged↗

PubMed1997

Impact of infecting dose on severity of disease in an outbreak of food-borne Salmonella enteritidis.

We conducted a cross-sectional study 72 h after a private dinner party, at which 33/59 participants (attack rate 56%) became infected with Salmonella enteritidis, phage type 6. All were interviewed and stool samples were obtained from 55 persons (93%). Only 2/33 cases were asymptomatic (6%). The median incubation period was 21 h. 14 of the cases (42%) were admitted to hospital. A significant association was found between infection and 1 of the egg-containing dishes (kabab). Cross-contamination to other dishes was likely. As an indirect measure of infecting dose, all persons were divided into exposure groups according to self-reported amount of consumed kabab, which was associated with risk of becoming ill (p = 0.00002) and the risk of hospitalization (p = 0.0005). Among the symptoms experienced by the patients, only fever was significantly associated with the amount of consumed kabab (p = 0.008). The present data suggest an existence of a dose-effect relationship in infections with S. enteritidis, phage type 6.

Adolescent↗