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Biomedical subjects

P Lips

Publications and source records attributed to P Lips.

At least 91 records · Page 5Linked to original sources
PubMed1998

Response of normal and osteoporotic human bone cells to mechanical stress in vitro.

Bone adapts to mechanical stress, and bone cell cultures from animal origin have been shown to be highly sensitive to mechanical stress in vitro. In this study, we tested whether bone cell cultures from human bone biopsies respond to stress in a similar manner as animal bone cells and whether bone cells from osteoporotic patients respond similarly to nonosteoporotic donors. Bone cell cultures were obtained as outgrowth from collagenase-stripped trabecular bone fragments from 17 nonosteoporotic donors between 7 and 77 yr of age and from 6 osteoporotic donors between 42 and 72 yr of age. After passage, the cells were mechanically stressed by treatment with pulsating fluid flow (PFF; 0.7 +/- 0.03 Pa at 5 Hz for 1 h) to mimic the stress-driven flow of interstitial fluid through the bone canaliculi, which is likely the stimulus for mechanosensation in bone in vivo. Similar to earlier studies in rodent and chicken bone cells, the bone cells from nonosteoporotic donors responded to PFF with enhanced release of prostaglandin E2 (PGE2) and nitric oxide as well as a reduced release of transforming growth factor-beta (TGF-beta). The upregulation of PGE2 but not the other responses continued for 24 h after 1 h of PFF treatment. The bone cells from osteoporotic donors responded in a similar manner as the nonosteoporotic donors except for the long-term PGE2 release. The PFF-mediated upregulation of PGE2 release during 24 h of postincubation after 1 h of PFF was significantly reduced in osteoporotic patients compared with six age-matched controls as well as with the whole nonosteoporotic group. These results indicate that enhanced release of PGE2 and nitric oxide, as well as reduced release of TGF-beta, is a characteristic response of human bone cells to fluid shear stress, similar to animal bone cells. The results also suggest that bone cells from osteoporotic patients may be impaired in their long-term response to mechanical stress.

Adolescent↗
PubMed1998

Predictors for falls and fractures in the Longitudinal Aging Study Amsterdam.

The objective of this study was to identify easily measurable predictors for falls, recurrent falls, and fractures using a population-based prospective cohort study of 1469 elderly, born before 1931, in three regions of the Netherlands. The baseline at-home interview was in 1992. In 1995, falls experienced in the preceding year and fractures over the preceding 38-month period were registered. In a period of 1 year, 32% of the participants fell at least once, and 15% fell two or more times. The rate of recurrent falls was similar in men and women up until the age of 75 years. The total number of fractures was 85, including 23 wrist fractures, 12 hip fractures, and 9 humerus fractures. The incidence density per 1000 person-years for any fracture was 25.1 (95% confidence interval [CI], 18.9-31.4) for women and 8.2 (95% CI, 4.5-12.0) for men, respectively. Multiple logistic regression identified urinary incontinence, impaired mobility, use of analgetics, and use of antiepileptic drugs as the predictors most strongly associated with recurrent falls. Female gender, living alone, past fractures, inactivity, body height, and use of analgetics proved to be the predictors most strongly associated with fractures. The probabilities of recurrent falls were 4.7% (95% CI, 2.9-7.5%) to 59. 2% (95% CI, 24.1-86.9%) with zero to four predictors, respectively. The probability of fractures ranged from 0.0% (95% CI, 0.0-0.4%) without any of the identified predictors to 12.9% (95% CI, 4.4-32. 2%) with all six predictors present. Our study shows that the risk of recurrent falls and of fractures can be predicted using up to, respectively, four and six easily measurable predictors. This study emphasizes the importance of impaired mobility and inactivity as predictors for falls and fractures.

Accidental Falls↗
PubMed1998

Intestinal calcium absorption and bone metabolism in young adult men with childhood-onset growth hormone deficiency.

Suboptimal growth hormone (GH) replacement therapy during childhood is a major cause of osteopenia in young adults with childhood-onset GH deficiency (CO-GHD). This is primarily attributed to reduced bone formation in childhood. It is currently not known whether GHD also has adverse effects on bone metabolism in adult life. To examine the impact of GHD on calcium and bone metabolism in adults, we evaluated 50 men with CO pituitary failure at a mean age of 28.2+/-4.5 years, i.e., 8.8+/-4.1 years after the discontinuation of previous GH treatment for short stature. Thirty-three patients had multiple pituitary hormone deficiencies (MPHD) for which they received conventional replacement therapy, seventeen patients had isolated GHD (IGHD), and forty-nine age-matched men served as controls. Intestinal calcium absorption, serum calcium concentration, serum phosphate levels, and renal calcium and phosphate excretion were normal in IGHD and MPHD patients. IGHD patients had marginally elevated serum levels of the carboxy-terminal cross-linked telopeptide of type I collagen (ICTP: 5.0+/-1.2 vs. 4.2+/-1.2 microg/l, p < 0.05), but other indices of bone turnover were normal. In contrast, MPHD patients had reduced levels of the carboxy-terminal propeptide of type I procollagen (PICP: 137+/-76 vs. 179+/-72 microg/l, p < 0.01), elevated serum ICTP levels (6.0+/-3.8 vs. 4.2+/-1.2 microg/l, p < 0.001), and reduced serum 1,25-dihydroxyvitamin D levels (55.1+/-16.7 vs. 73.0+/-23.0 pmol/l, p < 0.001). Multivariate regression analysis showed that the serum levels of bone resorption and bone formation markers in MPHD patients were correlated with the hydrocortisone, thyroxine, and testosterone replacement doses. There was no relationship with serum insulin-like growth factor I concentration. Panhypopituitary adults receiving conventional hormone replacement therapy are at risk to develop osteopenia either caused by reduced bone formation or by increased bone resorption activity. Predominantly, these abnormalities result from nonoptimal thyroid, gonadal, or adrenal hormone replacement therapy. GHD is not an important factor. In adults, GHD does not adversely affect intestinal calcium absorption or bone formation activity. Bone resorption activity may be slightly higher than normal, but the abnormality is too small to expect substantial bone loss as a consequence of GHD.

Adult↗
PubMed1998

Ultraviolet irradiation corrects vitamin D deficiency and suppresses secondary hyperparathyroidism in the elderly.

The objective of this study was to compare the effect of ultraviolet radiation (UV) and oral vitamin D3 on the vitamin D status and parathyroid hormone (PTH) concentration in elderly nursing home patients. The design of the study was a randomized clinical trial. The setting was a psychogeriatric nursing home. Subjects included 45 female psychogeriatric patients with a mean age of 85 years. Exclusion criteria were going outdoors more than once a week and the presence of actinic or cancer skin lesions. Intervention was random allocation of UV-B irradiation at half the minimal erythemal dose of the lower back, three times per week during 12 weeks (UV-B), or oral vitamin D3 400 IU/day during 12 weeks (VIT-D), or no treatment (CONTR). Main outcome measures were change in fasting serum levels of vitamin D metabolites at 0, 2, 4, 8, and 12 weeks in the treatment groups, compared with the control group. PTH(1-84) was measured at 0 and 12 weeks. Baseline serum 25-hydroxyvitamin D (25(OH)D) was lower than 30 nmol/l in 95% of the participants. It increased to a median value of around 60 nmol/l after 12 weeks both in the UV-B and VIT-D groups, whereas there was no change in the CONTR group. Serum 1,25-dihydroxyvitamin D increased significantly in the UV-B group. Serum calcium increased significantly in both treatment groups. Serum PTH decreased more than 30% in both treatment groups (p < 0.001), whereas there was no significant change in the control group. Irradiation with UV-B in the very elderly for a few minutes per day leads to adequate improvement of the vitamin D status. It is as effective as oral vitamin D3 in increasing serum 25(OH)D and suppressing secondary hyperparathyroidism.

Administration, Oral↗
PubMed1997

Epidemiology and predictors of fractures associated with osteoporosis.

Approximately 40 in 100 women will experience one or more fractures after the age of 50 years. At 50 years for women the lifetime risk is 17.5% for hip fracture, 16% for vertebral fracture, and 16% for Colles' fracture; for men, the respective lifetime risks are 6%, 5%, and 2.5%. The incidence of hip fractures has increased in recent years in most but not all European countries, partly as a result of the aging of the population. However, the age-adjusted incidence has also increased in several countries. The age-adjusted incidence of hip fractures varies greatly between European countries; in women incidence varies from about 50 per 10,000 women in Malta and Poland to 500 per 10,000 in Sweden. In addition, the sex ratio (female:male) varies from 1.6 in Poland to 4.2 in Iceland. A proportion of this large variation may be the result of underreporting of cases, although most European countries now have an adequate hospital registration. The prevalence of vertebral deformities also shows geographic variation. In the multinational European Vertebral Osteoporosis Study, a population-based study, the prevalence of vertebral deformities was similar among men and women at ages 65-69 years (12-13%); at younger ages the prevalence was higher in men than women, whereas the reverse was true at older ages. Incidence data on vertebral fractures are scarce because a large proportion of vertebral fractures are not clinically diagnosed. Prospective epidemiologic studies indicate that bone mineral density (BMD) is the single best predictor of fractures in perimenopausal women. Historic risk factors do not predict bone mass (or fractures) with sufficient precision to be useful in assessment of fracture risk or BMD. However, the presence of one vertebral fracture doubles the risk of future vertebral fracture as assessed by a BMD measurement. At advanced ages, other risk factors may be more important, such as the risk of falling, and combinations of risk factors for falls and low BMD may predict hip fractures. Risk factor assessment is currently of less value for the prediction of other fractures, such as vertebral or Colles' fracture. Determining the causes of the large geographic differences in hip fracture incidence and the large differences in sex ratios for hip fractures in European countries could lead to identification of hitherto unknown risk factors and provide clues for prevention of fractures. Many risk factors cannot be prevented or modified; however, these risk factors (for example, family history, past fracture, and visual loss) can identify risk groups amenable to drug treatment or to preventive measures such as protective hip pads or environmental changes. Assessment of risk factors and definition of risk profiles are important steps toward the prevention of fractures in the elderly.

Europe↗
PubMed1997

Quality of life as outcome in the treatment of osteoporosis: the development of a questionnaire for quality of life by the European Foundation for Osteoporosis.

The morbidity of osteoporosis is caused by fractures. Vertebral fractures lead to pain and disability and a decrease in quality of life. A Working Party of the European Foundation for Osteoporosis has developed a specific questionnaire for patients with established vertebral osteoporosis. This questionnaire is intended for use in clinical trials. The questionnaire consists of questions and visual analogue scales in the following domains: pain, activities of daily living, jobs around the house, mobility, leisure and social activities, general health perception and mood. The questionnaire has been translated from English into French, German, Italian, Hebrew, Swedish and Dutch. The questionnaire is currently being validated in a multicentre study involving patients with stable osteoporosis and control subjects. Preliminary results indicate that the reproducibility is sufficient and that the questionnaire is able to discriminate between patients with vertebral osteoporosis and control subjects.

Activities of Daily Living↗
PubMed1997

Orientation of the trabecular pattern of the distal radius around the menopause.

The trabecular pattern depicted on radiographs of the distal radius of women around the menopause is analysed by a new method to measure orientation. It is shown that the trabecular pattern on radiographs of the distal radius is aligned preferentially along the axial direction and to a lesser extent along the transverse direction. Two minima of orientation are found at 60 degrees off the axial direction. A significant correlation is found between the average value of the orientation in the radius and the average lumbar bone mineral density. It is known that the bone mineral content decreases around the menopause. Previous reports on the present images describe several features that were found to be related to bone mineral content and to time. The orientation of the trabecular pattern, however, is found to be independent of time, at least during the two years of the investigation. Therefore, it is concluded that the orientation of the radiographic trabecular pattern tends to remain stable even if some features of the pattern evolve. Previous studies on radiographs of the radius of children and elderly women and men provide evidence for the tendency of orientation to remain stable not only in women around the menopause, but also in men and women during the entire adult life.

Analysis of Variance↗
PubMed1997

Agenesis of the corpus callosum associated with paroxysmal hypothermia: Shapiro's syndrome.

Spontaneous recurrent hypothermia and hyperhidrosis associated with agenesis of the corpus callosum was first described by Shapiro and Plum in 1967. Since then, several cases with similar symptoms (now known as Shapiro's syndrome or spontaneous periodic hypothermia) have been described. We report another case of this syndrome in a 21-year-old-man, and discuss possible pathogenetic mechanisms and therapeutic approaches.

Adult↗
PubMed1997

The effect of growth hormone (GH) on histomorphometric indices of bone structure and bone turnover in GH-deficient men.

We investigated the effects of GH on bone structure and turnover by histomorphometry in GH-deficient adults. Therefore, transiliac bone biopsies were obtained before and after 1 yr of treatment in 36 GH-deficient men (mean age, 28 +/- 4 yr). Thirteen patients had isolated GH deficiency and 23 patients had multiple pituitary hormone deficiencies. Patients were randomly assigned to four treatment groups. Groups 1, 2, and 3 received 1, 2, and 3 IU/m2/day (0.35, 0.69, and 1.3 mg/m2/day) [corrected] GH, respectively, and the fourth group received placebo for the first 6 months and 2 IU/m2/day (5.8 mg/m2/day) GH for the subsequent 6 months. GH treatment resulted in an increase of cortical thickness from 0.98 +/- 0.27 to 1.20 +/- 0.35 mm (P = 0.005), but trabecular bone volume did not change. Bone formation variables increased significantly: osteoid surface increased from 8.5 +/- 5.3 to 15.5 +/- 6.1% (P = 0.0002), mineralizing surface increased from 6.7 +/- 2.5 to 10.8 +/- 4.4% (P = 0.0002), and bone formation rate increased from 0.04 +/- 0.02 to 0.08 +/- 0.04 mm3/mm2/day (P = 0.0001). Eroded surface did not change, but osteoclast number increased from 0.6 +/- 0.5 to 1.25 +/- 0.5 Oc/mm2 (P = 0.0001). The relative formation period increased significantly (P = 0.001), whereas the resorption period, including reversal phase, decreased from 65 to 40 days (P = 0.02). Activation frequency increased from 0.39 +/- 0.17 to 0.74 +/- 0.34 y(-1) (P = 0.0001). These data indicate a stimulated bone turnover as a result of GH treatment and a shorter resorption and reversal time. The increased turnover did not result in an increased trabecular bone volume, but the cortical thickness increased significantly.

Adult↗
PubMed1997

The effect of vitamin D supplementation on the bone mineral density of the femoral neck is associated with vitamin D receptor genotype.

Recent studies suggest that variations of the vitamin D receptor (VDR) gene are related to bone mineral density (BMD). In this study, we examined the effect of vitamin D3 supplementation on BMD at the femoral neck in relation to VDR genotype. We analyzed 81 women, age 70 years and over, who participated in a placebo-controlled clinical trial on the effect of vitamin D3 supplementation (400 IU daily for at least 2 years) on BMD and fracture incidence. VDR genotype was based on the presence (b) or absence (B) of the BsmI restriction site. Mean BMD of the right and left femoral neck was measured at baseline and after 1 and 2 years. Dietary calcium, body mass index, and years since menopause were assessed at baseline while biochemical markers were measured at baseline and after 1 year. There was no difference among the BB, Bb, and bb genotype for baseline measurements of BMD at the femoral neck (mean and SD, g/cm2: 0.70 (0.10), 0.71 (0.12), and 0.69 (0.10), respectively), nor for any of the biochemical indices. The mean increase of BMD in the vitamin D group relative to the placebo group, expressed as percentage of baseline BMD, was significantly higher (p = 0.03) in the BB (delta BMD: 4.4%, p = 0.04) and Bb genotype (delta BMD: 4.2%, p = 0.007) compared with the bb genotype (delta BMD: -0.3%, p = 0.61). No significant changes were found for any of the other measured parameters. The VDR genotype-dependent effect of vitamin D supplementation in these elderly subjects suggest a functional involvement of VDR gene variants in determining BMD.

Absorptiometry, Photon↗
PubMed1996

Falls in the elderly: a prospective study of risk factors and risk profiles.

In this prospective study, the authors determined intrinsic risk factors for falls and recurrent falls and constructed a risk profile that indicated the relative contribution of each risk factor and also estimated the probabilities of falls and recurrent falls. In 1992, over a 28-week period, falls were recorded among 354 elderly subjects aged 70 years or over who were living in homes or apartments for the elderly in Amsterdam and the vicinity. During the study period, 251 falls were reported by 126 subjects (36%), and recurrent falls (> or =2 falls) were reported by 57 subjects (16%). Associations of falls and recurrent falls with potential risk factors were identified in logistic regression models. Mobility impairment regarding one or more of the tested items (i.e., impairment of balance, leg-extension strength, and gait) was associated with falls (adjusted odds ratio (OR) =2.6) and was strongly associated with recurrent falls (OR = 5.0). Dizziness upon standing was associated with falls (OR = 2.1) and recurrent falls (OR = 2.1). However, several risk factors were associated with recurrent falls only: history of stroke (OR = 3.4), poor mental state (OR = 2.4), and postural hypotension (OR = 2.0). The authors constructed a risk profile for recurrent falls that included the five risk factors mentioned above. Inclusion of all risk factors in the profile implied an 84% probability of recurrent falls over a period of 28 weeks, compared with 3% when no risk factor was present. The probability of recurrent falls ranged only from 11% to 29% when predicted by number of falls occurring in the previous year. Physical activity, use of high-risk medication, and the use of vitamin D3, which was randomly allocated to the participants, were not strongly related to either falls or recurrent falls. In conclusion, a large range of probabilities of falls, especially of recurrent falls, was estimated by the risk profiles, in which mobility impairment was the major risk factor. Recurrent fallers may therefore be especially amenable to prevention based on mobility improvement.

Accidental Falls↗
PubMed1996

Vitamin D supplementation and fracture incidence in elderly persons. A randomized, placebo-controlled clinical trial.

OBJECTIVE: To determine whether vitamin D supplementation decreases the incidence of hip fractures and other peripheral bone fractures. DESIGN: Prospective, double-blind trial. SETTING: Community setting (Amsterdam and surrounding area). PATIENTS: 2578 persons (1916 women, 662 men) 70 years of age and older (mean age +/- SD, 80 +/- 6 years) living independently, in apartments for elderly persons, or in homes for elderly persons. INTERVENTION: Participants were randomly assigned to receive either vitamin D3, 400 IU in one tablet daily, or placebo for a maximum of 3.5 years. MEASUREMENTS: Dietary calcium intake and serum 25-hydroxyvitamin D [25(OH)D] were estimated in a subset of participants. During follow-up, attention was concentrated on hip fractures and other peripheral fractures. The maximal follow-up period was 4 years. The results were evaluated by survival analysis. RESULTS: Mean dietary calcium intake from dairy products was 868 mg/d. Mean serum 25(OH)D concentration in the third year of the study was 23 nmol/L in the placebo group and 60 nmol/L in the vitamin D group. Median follow-up was 3.5 years, and total follow-up was 8450 patient-years. During follow-up, 306 persons in the placebo group and 282 persons in the vitamin D group died (P = 0.20). Hip fractures occurred in 48 persons in the placebo group and 58 persons in the vitamin D group (P = 0.39, intention-to-treat analysis). Other peripheral fractures occurred in 74 persons in the placebo group and 77 persons in the vitamin D group (P = 0.86). CONCLUSION: Our results do not show a decrease in the incidence of hip fractures and other peripheral fractures in Dutch elderly persons after vitamin D supplementation.

Aged↗
PubMed1996

1,25-dihydroxyvitamin D3-mediated transforming growth factor-beta release is impaired in cultured osteoblasts from patients with multiple pituitary hormone deficiencies.

To evaluate the osteoblastic function in patients with multiple pituitary hormone deficiencies (M-PHD) and with isolated growth hormone deficiency (I-GHD), bone cells were cultured and the effects of 10(-8) M 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) on parameters of cell proliferation, osteoblastic differentiation, and local paracrine regulation were measured. Three days of 1,25(OH)2D3 treatment increased alkaline phosphatase activity and osteocalcin release but inhibited [3H]thymidine incorporation in all cell cultures from patients as well as from controls. In addition, 1,25(OH)2D3 increased the release of both total and active transforming growth factor-beta (TGF-beta) in bone cells from controls by, respectively, 4.9- and 3.2-fold and in bone cells from I-GHD by 5.1- and 1.5-fold, respectively. However, in bone cells from M-PHD, the stimulation of total TGF-beta release was significantly lower (1.3-fold) than in control and I-GHD cells, and active TGF-beta release was not stimulated at all. One year of supplementation with human growth hormone did not improve this deficient TGF-beta release in bone cells from M-PHD. We conclude that cultured bone cells from I-GHD and M-PHD show a normal response to 1,25(OH)2D3 regarding cell proliferation and osteoblastic differentiation, which implicates a normal 1,25(OH)2D3-receptor function. In cells from controls and I-GHD, 1,25(OH)2D3 enhanced both total and active TGF-beta release. However, bone cells from M-PHD showed a deficient TGF-beta response to 1,25(OH)2D3. These results suggest that the regulation of TGF-beta production is a major paracrine factor involved in hypopituitarism.

Adult↗
PubMed1996

The effect of androgen treatment on bone metabolism in female-to-male transsexuals.

Histomorphometry was performed in iliac crest biopsies from 15 female-to-male (F-M) transsexuals with a mean age of 30 +/- 6.1 (SD) years. At the time of study, they had been treated with parenteral testosterone esters (250 mg/2 weeks) or oral testosterone undecanoate (160 mg/day). The median androgen treatment duration was 39 months. The patients had undergone hysterectomy and bilateral ovariectomy. The bone biopsy was obtained after double tetracycline labeling. Histomorphometric results were compared with data from 8 postmenopausal women and with data from 11 healthy men who had died suddenly. Dynamic parameters were compared with data from the literature. The biochemical picture was characterized by serum testosterone concentrations lower than in eugonadal men and estradiol concentrations lower than in eugonadal women and elevated gonadotrophin levels. The bone mineral density in the F-M transsexuals was as expected for age (Z-score -0.31 +/- 1.49). Cortical thickness was significantly higher in F-M transsexuals than in both control groups. Trabecular bone structure was similar in F-M transsexuals and both control groups. The bone formation parameters were generally lower in F-M transsexuals than in the control groups. The eroded surface was lower in F-M transsexuals than in postmenopausal women. The low bone turnover and preservation of trabecular bone is consistent with the assumption that testosterone treatment protects the bone in these F-M transsexuals from the deleterious effects of estrogen deficiency. The increased cortical thickness suggests an anabolic effect of the testosterone treatment.

Adult↗