The available literature on cost benefit, cost effectiveness and cost utility of different drug a... more 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.
Maturation of macrophages to osteoclasts requires the presence of marrow stromal cells or osteobl... more Maturation of macrophages to osteoclasts requires the presence of marrow stromal cells or osteoblasts. Most calcitropic hormones act indirectly on osteoclasts through receptors on neighbouring osteoblasts. The discovery of osteoprotegerin (OPG), the receptor activator of nuclear factor-kappa b ligand (RANKL), and its receptor (RANK) has elucidated these phenomena. It appears that osteoclast differentiation, activity, and survival are regulated by the proportion of inhibiting OPG to stimulating RANKL. OPG and RANKL are produced by osteoblasts, whereas RANK is located to the osteoclasts. Treatment with OPG inhibits bone resorption in postmenopausal women. Mutations in the system may be responsible for focal skeletal disorders. The discovery opens up for new treatment opportunities in postmenopausal and steroid-induced osteoporosis, Paget's disease, hypercalcaemia, and rheumatoid arthritis.
Autosomal dominant osteopetrosis is radiographically characterized by universal osteosclerosis, p... more Autosomal dominant osteopetrosis is radiographically characterized by universal osteosclerosis, primarily involving the axial skeleton, and by symmetrical affections of the long bones without modeling defects. Based on standard radiographs, it is possible to describe two different subtypes with different clinical, biochemical, and histologic manifestations. Type I is radiographically characterized by pronounced osteosclerosis of the cranial vault, whereas Type II has end-plate thickening of the vertebrae (Rugger-Jersey spine) and endobones in the pelvis. Both types are strictly family related and seen in childhood. Combined radiogrammetric, biochemical, and histologic investigations indicate states of defective bone resorption, whereas bone formation seems to be normal in both types of patients. Patients with autosomal dominant osteopetrosis are often asymptomatic, and the diagnosis may be reached by chance. However, by systematic investigations, nearly all patients have manifestations related to the disorder. Symptoms are progressive with age, and correlated with osteosclerosis. The fracture frequency is increased in Type II patients, and normal in Type I, where biomechanical investigations have shown normal, or even increased trabecular bone strength. Treatment has been symptomatic. A rational treatment consists of stimulation of bone resorption, in combination with inhibition of bone formation if possible.
Gitelmans syndrome represents the clinical manifestations of inactivating mutations in the gene e... more Gitelmans syndrome represents the clinical manifestations of inactivating mutations in the gene encoding for the thiazide sensitive sodium chloride cotransporter in the distal convoluted tubule. Thus, the biochemical characteristics resemble those seen with thiazide diuretics: hypokalemia, hypomagnesemia, hypocalcuria, metabolic alkalosis and blood pressure in the low normal range. Until the genetic background was clarified in 1996, Gitelman's syndrome was often mistaken for Bartter's syndrome, which is now attributed to defects in the ion transportation system in the thick ascending limb of Henle's loop. In Bartter's syndrome, hypomagnesemia is not a constant finding and urinary calcium excretion is normal or high. Bartter,s syndrome is often diagnosed neonatally and followed by growth retardation and nefrocalcinosis. Gitelman's syndrome is typically diagnosed accidentally (hypokalemia) in adolescents or adults and the course is benign. If present, the most prominent symptoms are muscular fatigue or occasional tetany. Treatment includes magnesium and potassium supplements and potassium saving diuretics.
To analyze fracture risk and bone mineral density in patients with eating disorders (anorexia ner... more To analyze fracture risk and bone mineral density in patients with eating disorders (anorexia nervosa, bulimia nervosa, and other eating disorders). Clinical overview. Bone mineral density is decreased and fracture risk increased in patients with anorexia nervosa. In patients with bulimia nervosa, bone mineral is only marginally decreased and fracture risk marginally increased. In patients with other eating disorders (eating disorders not otherwise specified), bone mineral density is decreased and fracture risk increased. Fracture risk is increased in patients with eating disorders. An eating disorder should be suspected in severely underweight young individuals (primarily girls) presenting with fractures, especially low-energy fractures.
Background. Studies on bone effects of long-term substitution therapy with levothyroxine (LT4) ha... more Background. Studies on bone effects of long-term substitution therapy with levothyroxine (LT4) have shown discrepant results. Previous studies have, however, not evaluated volumetric bone mineral densities (vBMD), bone structure, and strength using high resolution peripheral quantitative computed tomography (HR-pQCT) and finite element analysis (FEA). Using a cross-sectional design, we aimed to determine whether BMD, structure, and strength are affected in hypothyroid patients on LT4 substitution therapy. Methods. We compared 49 patients with well-substituted hypothyroidism with 49 age- and gender-matched population based controls. Areal BMD was assessed by DXA, vBMD and bone geometry by HR-pQCT, and bone strength by FEA. Results. Patients had been thyroidectomized due to thyroid cancer (10%) and nontoxic (33%) or toxic goiter (57%). 82% were women. TSH levels did not differ between groups, but patients had significantly higher levels of T4 (p < 0.001) and lower levels of T3 (p &...
Pseudohypoparathyroidism (PHP) is caused by a mutation within the GNAS gene or upstream of the GN... more Pseudohypoparathyroidism (PHP) is caused by a mutation within the GNAS gene or upstream of the GNAS complex locus. It is characterized by target organ resistance to PTH, resulting in hypocalcaemia and hyperphosphataemia. Studies in patients with PHP are limited. We sought to identify all patients in Denmark with PHP and access their mortality data and risk of complications. Patients were identified through the Danish National Patient Registry and a prescription database, with subsequent validation by investigation of patient charts. For each case, three age- (±2 years) and gender-matched controls were randomly selected from the general background population. We identified a total of 60 cases, equal to a prevalence of 1·1/100 000 inhabitants. The average age at diagnosis was 13 years (range 1-62 years), and 42 were women. Only 14 patients had an identified mutation in the GNAS1 gene. Compared with controls, patients with PHP had an increased risk of neuropsychiatric disorders (P <...
Melatonin is often used as a sleeping aid in elderly adults. As previous studies suggest a protec... more Melatonin is often used as a sleeping aid in elderly adults. As previous studies suggest a protective role of melatonin against osteoporosis, it is important to document its safety. Treatment should not cause any hangover effect that could potentially lead to falls and fractures. We therefore aimed to evaluate the effect of melatonin on balance- and muscle function. In a double-blind placebo-controlled study, we randomized 81 postmenopausal women with osteopenia to receive 1 or 3 mg melatonin, or placebo nightly for 12 months. Postural balance as well as muscle function was measured. In addition, we assessed quality of life and sleep at baseline and after 12 months treatment. Compared to placebo, one-year treatment with melatonin did not affect postural balance or risk of falls. Furthermore, no significant changes between groups were observed in muscle strength in neither upper- nor lower extremities. Treatment did not affect quality of life or sleep. However, in the subgroup of wom...
To assess the effects of surgery compared with conservative treatment (no surgery) for primary hy... more To assess the effects of surgery compared with conservative treatment (no surgery) for primary hyperparathyroidism. Cohort study. Nationwide Danish cohort. 3213 patients, mean age 61 (SD 16) years, with a diagnosis of primary hyperparathyroidism between 1980 and 1999. 1934 (60%) underwent surgery and 1279 (40%) were treated conservatively. Occurrence of fractures, osteoporosis, kidney or urinary tract stones, acute myocardial infarction, angina pectoris, cardiac arrhythmias, arterial hypertension, heart failure, stroke, acute pancreatitis, stomach or duodenal ulcers, muscle pain, malignant diseases, psychiatric disorders, and mortality. At diagnosis of primary hyperparathyroidism, patients who subsequently underwent surgery had a lower prevalence of previous fracture (odds ratio 0.64, 95% confidence interval 0.51 to 0.80), acute myocardial infarction (0.59, 0.42 to 0.83), stroke (0.57, 0.37 to 0.88), psychiatric disorders (0.54, 0.31 to 0.94), and painful muscle disorders (0.44, 0.26 to 0.76), whereas kidney stones (2.49, 1.93 to 3.23) and acute pancreatitis (2.77, 1.33 to 5.76) were more prevalent. After diagnosis, the risks of fractures (hazards ratio 0.69, 0.56 to 0.84) and gastric ulcers (0.59, 0.41 to 0.84) were lower in patients treated surgically than those treated conservatively. Events involving kidney or urinary tact stones were more prevalent in patients treated surgically than patients treated conservatively (1.87, 1.30 to 2.68). Mortality was lower in patients treated surgically (0.65, 0.57 to 0.73). Patients treated surgically for primary hyperparathyroidism have a lower prevalence of fractures and gastric ulcers than patients treated conservatively. The type of treatment had no effect on the occurrence of cardiovascular events.
The available literature on cost benefit, cost effectiveness and cost utility of different drug a... more 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.
Maturation of macrophages to osteoclasts requires the presence of marrow stromal cells or osteobl... more Maturation of macrophages to osteoclasts requires the presence of marrow stromal cells or osteoblasts. Most calcitropic hormones act indirectly on osteoclasts through receptors on neighbouring osteoblasts. The discovery of osteoprotegerin (OPG), the receptor activator of nuclear factor-kappa b ligand (RANKL), and its receptor (RANK) has elucidated these phenomena. It appears that osteoclast differentiation, activity, and survival are regulated by the proportion of inhibiting OPG to stimulating RANKL. OPG and RANKL are produced by osteoblasts, whereas RANK is located to the osteoclasts. Treatment with OPG inhibits bone resorption in postmenopausal women. Mutations in the system may be responsible for focal skeletal disorders. The discovery opens up for new treatment opportunities in postmenopausal and steroid-induced osteoporosis, Paget&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease, hypercalcaemia, and rheumatoid arthritis.
Autosomal dominant osteopetrosis is radiographically characterized by universal osteosclerosis, p... more Autosomal dominant osteopetrosis is radiographically characterized by universal osteosclerosis, primarily involving the axial skeleton, and by symmetrical affections of the long bones without modeling defects. Based on standard radiographs, it is possible to describe two different subtypes with different clinical, biochemical, and histologic manifestations. Type I is radiographically characterized by pronounced osteosclerosis of the cranial vault, whereas Type II has end-plate thickening of the vertebrae (Rugger-Jersey spine) and endobones in the pelvis. Both types are strictly family related and seen in childhood. Combined radiogrammetric, biochemical, and histologic investigations indicate states of defective bone resorption, whereas bone formation seems to be normal in both types of patients. Patients with autosomal dominant osteopetrosis are often asymptomatic, and the diagnosis may be reached by chance. However, by systematic investigations, nearly all patients have manifestations related to the disorder. Symptoms are progressive with age, and correlated with osteosclerosis. The fracture frequency is increased in Type II patients, and normal in Type I, where biomechanical investigations have shown normal, or even increased trabecular bone strength. Treatment has been symptomatic. A rational treatment consists of stimulation of bone resorption, in combination with inhibition of bone formation if possible.
Gitelmans syndrome represents the clinical manifestations of inactivating mutations in the gene e... more Gitelmans syndrome represents the clinical manifestations of inactivating mutations in the gene encoding for the thiazide sensitive sodium chloride cotransporter in the distal convoluted tubule. Thus, the biochemical characteristics resemble those seen with thiazide diuretics: hypokalemia, hypomagnesemia, hypocalcuria, metabolic alkalosis and blood pressure in the low normal range. Until the genetic background was clarified in 1996, Gitelman&amp;amp;amp;amp;amp;amp;amp;amp;#39;s syndrome was often mistaken for Bartter&amp;amp;amp;amp;amp;amp;amp;amp;#39;s syndrome, which is now attributed to defects in the ion transportation system in the thick ascending limb of Henle&amp;amp;amp;amp;amp;amp;amp;amp;#39;s loop. In Bartter&amp;amp;amp;amp;amp;amp;amp;amp;#39;s syndrome, hypomagnesemia is not a constant finding and urinary calcium excretion is normal or high. Bartter,s syndrome is often diagnosed neonatally and followed by growth retardation and nefrocalcinosis. Gitelman&amp;amp;amp;amp;amp;amp;amp;amp;#39;s syndrome is typically diagnosed accidentally (hypokalemia) in adolescents or adults and the course is benign. If present, the most prominent symptoms are muscular fatigue or occasional tetany. Treatment includes magnesium and potassium supplements and potassium saving diuretics.
To analyze fracture risk and bone mineral density in patients with eating disorders (anorexia ner... more To analyze fracture risk and bone mineral density in patients with eating disorders (anorexia nervosa, bulimia nervosa, and other eating disorders). Clinical overview. Bone mineral density is decreased and fracture risk increased in patients with anorexia nervosa. In patients with bulimia nervosa, bone mineral is only marginally decreased and fracture risk marginally increased. In patients with other eating disorders (eating disorders not otherwise specified), bone mineral density is decreased and fracture risk increased. Fracture risk is increased in patients with eating disorders. An eating disorder should be suspected in severely underweight young individuals (primarily girls) presenting with fractures, especially low-energy fractures.
Background. Studies on bone effects of long-term substitution therapy with levothyroxine (LT4) ha... more Background. Studies on bone effects of long-term substitution therapy with levothyroxine (LT4) have shown discrepant results. Previous studies have, however, not evaluated volumetric bone mineral densities (vBMD), bone structure, and strength using high resolution peripheral quantitative computed tomography (HR-pQCT) and finite element analysis (FEA). Using a cross-sectional design, we aimed to determine whether BMD, structure, and strength are affected in hypothyroid patients on LT4 substitution therapy. Methods. We compared 49 patients with well-substituted hypothyroidism with 49 age- and gender-matched population based controls. Areal BMD was assessed by DXA, vBMD and bone geometry by HR-pQCT, and bone strength by FEA. Results. Patients had been thyroidectomized due to thyroid cancer (10%) and nontoxic (33%) or toxic goiter (57%). 82% were women. TSH levels did not differ between groups, but patients had significantly higher levels of T4 (p < 0.001) and lower levels of T3 (p &...
Pseudohypoparathyroidism (PHP) is caused by a mutation within the GNAS gene or upstream of the GN... more Pseudohypoparathyroidism (PHP) is caused by a mutation within the GNAS gene or upstream of the GNAS complex locus. It is characterized by target organ resistance to PTH, resulting in hypocalcaemia and hyperphosphataemia. Studies in patients with PHP are limited. We sought to identify all patients in Denmark with PHP and access their mortality data and risk of complications. Patients were identified through the Danish National Patient Registry and a prescription database, with subsequent validation by investigation of patient charts. For each case, three age- (±2 years) and gender-matched controls were randomly selected from the general background population. We identified a total of 60 cases, equal to a prevalence of 1·1/100 000 inhabitants. The average age at diagnosis was 13 years (range 1-62 years), and 42 were women. Only 14 patients had an identified mutation in the GNAS1 gene. Compared with controls, patients with PHP had an increased risk of neuropsychiatric disorders (P <...
Melatonin is often used as a sleeping aid in elderly adults. As previous studies suggest a protec... more Melatonin is often used as a sleeping aid in elderly adults. As previous studies suggest a protective role of melatonin against osteoporosis, it is important to document its safety. Treatment should not cause any hangover effect that could potentially lead to falls and fractures. We therefore aimed to evaluate the effect of melatonin on balance- and muscle function. In a double-blind placebo-controlled study, we randomized 81 postmenopausal women with osteopenia to receive 1 or 3 mg melatonin, or placebo nightly for 12 months. Postural balance as well as muscle function was measured. In addition, we assessed quality of life and sleep at baseline and after 12 months treatment. Compared to placebo, one-year treatment with melatonin did not affect postural balance or risk of falls. Furthermore, no significant changes between groups were observed in muscle strength in neither upper- nor lower extremities. Treatment did not affect quality of life or sleep. However, in the subgroup of wom...
To assess the effects of surgery compared with conservative treatment (no surgery) for primary hy... more To assess the effects of surgery compared with conservative treatment (no surgery) for primary hyperparathyroidism. Cohort study. Nationwide Danish cohort. 3213 patients, mean age 61 (SD 16) years, with a diagnosis of primary hyperparathyroidism between 1980 and 1999. 1934 (60%) underwent surgery and 1279 (40%) were treated conservatively. Occurrence of fractures, osteoporosis, kidney or urinary tract stones, acute myocardial infarction, angina pectoris, cardiac arrhythmias, arterial hypertension, heart failure, stroke, acute pancreatitis, stomach or duodenal ulcers, muscle pain, malignant diseases, psychiatric disorders, and mortality. At diagnosis of primary hyperparathyroidism, patients who subsequently underwent surgery had a lower prevalence of previous fracture (odds ratio 0.64, 95% confidence interval 0.51 to 0.80), acute myocardial infarction (0.59, 0.42 to 0.83), stroke (0.57, 0.37 to 0.88), psychiatric disorders (0.54, 0.31 to 0.94), and painful muscle disorders (0.44, 0.26 to 0.76), whereas kidney stones (2.49, 1.93 to 3.23) and acute pancreatitis (2.77, 1.33 to 5.76) were more prevalent. After diagnosis, the risks of fractures (hazards ratio 0.69, 0.56 to 0.84) and gastric ulcers (0.59, 0.41 to 0.84) were lower in patients treated surgically than those treated conservatively. Events involving kidney or urinary tact stones were more prevalent in patients treated surgically than patients treated conservatively (1.87, 1.30 to 2.68). Mortality was lower in patients treated surgically (0.65, 0.57 to 0.73). Patients treated surgically for primary hyperparathyroidism have a lower prevalence of fractures and gastric ulcers than patients treated conservatively. The type of treatment had no effect on the occurrence of cardiovascular events.
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