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Biomedical subjects

S Ljunghall

Publications and source records attributed to S Ljunghall.

At least 37 records · Page 2Linked to original sources
PubMed2000

Hypocalcemia and parathyroid hormone secretion in critically ill patients.

OBJECTIVE: To investigate possible causes of hypocalcemia and to assess parathyroid hormone (PTH) secretion in intensive care unit (ICU) patients. DESIGN: Combined cross-sectional and prospective study. SETTING: ICU in a university hospital. PATIENTS: Thirteen patients with sepsis and 13 patients who underwent major surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Calcium metabolic indices were investigated during the first 24 hrs in the ICU and after 2 days. Eight of the surgical patients and five of the septic patients were subjected to a citrate/calcium infusion on day 1 in the ICU, to study the dynamics of PTH secretion. The blood ionized calcium (Ca2+) concentration was generally low in the septic patients (mean +/- SD, 1.03+/-0.08 mmol/L; reference value, 1.10-1.30) and increased, but not normalized, after 2 days. Hypocalcemia was only occasionally seen in the surgical patients. In the septic patients, urinary excretion of calcium was low; and, in both patient groups, elevated concentrations of two markers of bone resorption, deoxypyridinoline and ICTP (serum carboxy-terminal cross-linked telopeptide of type I collagen), were found. In cases of sepsis, the concentrations of proinflammatory cytokines were high (394+/-536 pg/mL for tumor necrosis factor-alpha and 5676+/-5190 pg/mL for interleukin-6, both normally <10-20). The Ca2+ concentration was inversely related to tumor necrosis factor-alpha and interleukin-6 (r2 = .35-.42; p<.01), as well as to procalcitonin (r2 = .71; p<.01). Despite normocalcemia in the surgical patients, serum PTH concentrations were elevated in both patient groups (97 and 109 ng/L) (reference value, <55 ng/L), both on day 1 and day 3 in the ICU. The citrate/calcium infusion revealed an increased secretory response of PTH to lowered Ca2+ concentrations in both groups of patients (p<.05), when compared with matched healthy controls. CONCLUSION: Hypocalcemia was common in septic ICU patients and was not the result of an increased urinary excretion of calcium or of an attenuated bone resorption, but seemed related to the inflammatory response. An increased PTH secretion was found in both patient groups.

APACHE↗
PubMed1999

Increased fracture rate in diabetes mellitus and females after renal transplantation.

BACKGROUND: Bone disease and fractures after organ transplantation pose severe clinical problems. About 20% of renal transplant patients have type 1 diabetes (IDDM). However, data are scarce in the literature about the occurrence of spontaneous fractures in IDDM patients posttransplantation. METHODS: In this cross-sectional study using a questionnaire and hospital records the prevalence of symptomatic bone disease was investigated in 193 renal transplanted patients with functioning renal grafts 6 months to 23 years after the transplantation. RESULTS: The frequency of IDDM was 18%. In the total group the rate of osteoporotic fractures posttransplantation was 17%, and the majority of fractures occurred within the first 3 years after the transplantation. A high rate of fractures, 40%, was noted in the diabetes group (P<0.001), compared with 11% in the nondiabetes group. Fractures seen in IDDM were often multiple and located mostly in the appendicular skeleton, i.e., in ankles and feet. Female gender was also associated with an elevated fracture rate, 23% (P<0.05). CONCLUSION: An increased incidence of osteoporotic fractures after renal transplantation was found in diabetic and female patients. The mechanism behind bone fragility in IDDM is multifactorial and despite a restored renal function bone disease may progress, and is probably enhanced by the immunosuppressive treatment.

Cross-Sectional Studies↗
PubMed1999

Oral-contraceptive use and risk of hip fracture: a case-control study.

BACKGROUND: Epidemiological studies indicate a protective effect of postmenopausal oestrogen therapy on the risk of osteoporotic fractures. Whether premenopausal oestrogen exposure in the form of oral contraceptives also reduces the risk of osteoporotic fractures remains uncertain. METHOD: We did a population-based case control study of hip fracture among Swedish postmenopausal women, 50-81 years of age, through mailed questionnaires and telephone interviews. Of those women who were eligible, 1327 (82.5%) cases and 3312 (81.6%) randomly selected controls responded. FINDINGS: 130 (11.6%) cases and 562 (19.1%) controls reported ever-use of oral contraceptives. Ever-use of oral contraceptives was associated with a 25% reduction in hip fracture risk (odds ratio 0.75 [95% CI 0.59-0.96]). Women who had ever used a high-dose pill (equivalent to > or = 50 microg ethinylestradiol per tablet) had a 44% lower risk for hip fracture than never-users (0.56 [0.42-0.75]). No overall trend was observed with duration of oral-contraceptive use, or time since last use. However, when making comparisons with women who have never used oral contraceptives, the odds ratios for hip-fracture were 0.69 (0.51-0.94) for use after age 40, 0.82 (0.57-1.16) for use at ages 30-39, and 1.26 (0.76-2.09) for use before age 30. INTERPRETATION: Our results imply that in postmenopausal women, oral-contraceptive use late in reproductive life may reduce the risk of hip fracture, although we recognise the limitations of the case-control method.

Adult↗
PubMed1999

Whole-body bone mineral measurements in 15-year-old Swedish adolescents.

Bone mineral area (BA), total bone mineral content (TBMC) and total bone mineral density (TBMD) were assessed by dual-energy X-ray absorptiometry (DXA) in 396 randomly selected, healthy 15-year-old Swedish boys and girls. The influence of body size, pubertal development, physical activity level (PAL), total energy expenditure (TEE), dietary intake of energy, calcium and vitamin D, and alcohol and smoking habits on TBMC and TBMD were examined in bi- and multivariate analyses. In bivariate analyses BA, TBMC and TBMD showed strong correlations with weight, height and TEE in both sexes. In boys but not in girls these bone variables were significantly correlated with dietary intakes of energy, calcium and vitamin D. No significant correlations were found between PAL and the three bone variables. In multivariate analyses with TBMC as dependent variable BA, height, weight and Tanner stages explained 88% and 87% of the variance in boys and girls respectively. In similar analyses with TBMD as dependent variable the corresponding figures were 50% and 54%. The major part of the variance in all these models was explained by BA, and only a few percent by all the other independent variables. No significant reduction was found when TEE or daily intakes of calcium or vitamin D were introduced into the models. These results illustrate the importance of including BA, weight and height as independent variables in regression models of TBMC to avoid spurious associations with other variables in the analyses. The results may also indicate that in normal Swedish adolescents environmental factors such as dietary intake of nutrients play a minor role as determinants of bone mineralization. High levels of physical activity and bone mineral measures possibly explain the lack of significant correlations between these variables and do not imply a lack of association.

Absorptiometry, Photon↗
PubMed1999

Differences in risk factor patterns between cervical and trochanteric hip fractures. Swedish Hip Fracture Study Group.

The two types of hip fracture--cervical and trochanteric femoral fractures--are generally considered together in etiologic studies. However, women with a trochanteric fracture may be more osteoporotic than those with cervical hip fractures, and have higher post-fracture mortality. To explore differences in risk factor patterns between the two types of hip fracture we used data from a large population-based case-control study in Swedish women, 50-81 years of age. Data were collected by questionnaire, to which more than 80% of subjects responded. Of the cases included, 811 had had a cervical fracture and 483 a trochanteric fracture during the study period; these cases were compared with 3312 randomly selected controls. Height and hormonal factors appeared to affect the risk of the two types of hip fracture differently. For every 5 cm of current height, women with a cervical fracture had an adjusted odds ratio (OR) of 1.23 (95% CI 1.15-1.32) compared with an OR of 1.06 (95% CI 0.97-1.15) for women with trochanteric fractures. Later menopausal age was protective for trochanteric fractures (OR 0.95, 95% CI 0. 91-0.99 per 2 years) but no such association was found for cervical fractures. Compared with never smokers, current smokers had an OR of 1.48 (95% CI 1.12-1.95) for trochanteric fractures and 1.22 (95% CI 0.98-1.52) for cervical fractures. Current hormone replacement therapy was similarly protective for both fracture types, but former use substantially reduced risk only for trochanteric fractures: OR 0. 55 (95% CI 0.33-0.92) compared with 1.00 (95% CI 0.71-1.39) for cervical fractures. These risk factor patterns suggest etiologic differences between the fracture types which have to be considered when planning preventive interventions.

Age Factors↗
PubMed1999

Decreased estradiol levels and free androgen index and elevated sex hormone-binding globulin levels in male idiopathic osteoporosis.

Estrogen deficiency is an important pathogenetic factor in female osteoporosis, and androgens are known to have anabolic effects on bone. In this study we have compared 12 men with idiopathic osteoporosis, age 27-55 years, with 12 age-matched men, with respect to serum levels of sex steroids, biochemical markers of bone turnover, bone density, and body composition. All subjects showed values within the normal range for all hormonal parameters. The patient group compared with the controls had significantly lower serum levels of estradiol (71 +/- 13 versus 85 +/- 14 pmol/liter, P < 0.03); estradiol/sex hormone-binding globulin (SHBG) ratio (22.4 +/- 12.1 versus 39.5 +/- 18.6 pmol/mg, P < 0.02); free androgen index (51.0 +/- 19.4 versus 74.1 +/- 33.1%, P < 0.05); and higher SHBG (3.7 +/- 1.6 versus 2.5 +/- 1.0 mg/liter; P < 0.04). The men with idiopathic osteoporosis had significantly lower body mass index (23.2 +/- 2.8 versus 25.9 +/- 3.3 kg/m2, P < 0.05); and a tendency to lower percentage of total body fat (14.2 +/- 5.5 versus 18.6 +/- 6.0%; P < 0.10) than the controls. Regression analyses revealed that bone mineral density in femoral neck correlated significantly and positively with the ratio estradiol/SHBG (r = 0.67; P < 0.04) and negatively with SHBG concentrations (r = -0.63; P < 0.04) in the group of patients. These findings could represent a pathogenetic mechanism in male idiopathic osteoporosis.

Absorptiometry, Photon↗
PubMed1999

Circulating ionized calcium and parathyroid hormone levels following coronary artery by-pass surgery.

In critically ill patients, hypocalcaemia is a common finding. Also variable derangements in the normally tight Ca2+-mediated control of the parathyroid hormone (PTH) secretion have been found. Utilizing coronary artery by-pass grafting (CABG) as a standardized model of severe trauma, 18 patients underwent determinations of blood levels of calcium, magnesium (Mg), ionized calcium (Ca2+), serum levels of intact PTH, procalcitonin (PCT) and the proinflammatory cytokines tumour necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6). Samples were collected before, directly after, the morning after and 5 days after surgery. A significant, but minor, decrease in blood Ca2+ levels (mean 0.04 mmol/L, p<0.05) was seen shortly after CABG, not accompanied by any significant change of serum PTH levels. This alteration of the Ca2+ control of the steady-state PTH levels contrasted with the maintenance of the PTH secretory response to a sequential citrate and calcium infusion (CiCa clamp), which was normal in two patients evaluated in the morning following surgery. Serum Mg levels were transiently increased after operation (+0.25 mmol/L, p<0.001) and correlated to the TNF-alpha (r=0.62, p <0.01) and PCT (r=0.67, p < 0.006) levels in the morning after surgery. Serum levels of IL-6 and TNF-alpha were significantly (p < 0.0001) increased immediately after surgery, while the peak in serum PCT levels (p < 0.001) occurred in the morning after CABG. Serum PTH levels correlated positively with IL-6 (r=0.68, p<0.008) 5 days after surgery. In conclusion, CABG caused a decrease in ionized calcium levels without a rise in steady-state PTH levels, but rapid changes in Ca2+ during CiCa clamping revealed a normal PTH secretory response. These findings might relate to elevated serum Mg levels, while a direct action of TNF-alpha or IL-6 on the PTH release seem less possible.

Aged↗
PubMed1999

Use of novel bone biopsy system to study molecular effects of growth hormone in human bone--a pilot study.

In this study, we have examined whether a novel bone biopsy system combined with reverse transcription-polymerase chain reaction (RT-PCR) or differential display PCR (ddPCR) can be used to detect specific mRNAs induced by growth hormone (GH) in human bone. In a 58-year-old man with complete GH deficiency as a result of empty sella, bone biopsies were taken before, and 5 and 24 h after administration of 24 recombinant human GH. Insulin-like growth factor binding protein-3 (IGFBP-3) mRNA levels in this patient, measured in a semiquantitative RT-PCR assay, increased about 40% 24 h after GH administration. This increase was not seen in a healthy control who did not receive GH, suggesting that the increase was an effect of GH rather than of the biopsy itself. Several differentially expressed mRNAs were detected by ddPCR. Thus, this pilot study suggests that our novel bone biopsy system may be suitable for in vivo studies of the molecular effects of substances with essential functions in human bone.

Base Sequence↗
PubMed1999

Evaluation of bone disease in multiple myeloma: a comparison between the resorption markers urinary deoxypyridinoline/creatinine (DPD) and serum ICTP, and an evaluation of the DPD/osteocalcin and ICTP/osteocalcin ratios.

Markers of bone metabolism were measured in 73 newly diagnosed myeloma patients and in age-matched controls. Correlations to bone disease on X-rays and survival were performed. In urine deoxypyridinoline/creatinine (DPD) and in serum carboxyterminal pyridinoline cross-linked telopeptide of type I collagen (ICTP), procollagen type I carboxy-terminal extension peptide (PICP) and osteocalcin were analyzed. The ratios DPD/osteocalcin and ICTP/osteocalcin were calculated. Skeletal X-ray findings were divided into no, limited and extensive bone involvement. DPD and ICTP levels were significantly elevated in patients compared to controls. Levels increased with advancing skeletal involvement. Serum osteocalcin was elevated in patients without visible bone disease. The level decreased with more advanced bone involvement. The finding of significantly elevated osteocalcin and ICTP levels in patients without bone involvement on X-rays indicates that bone markers might reflect bone disease better than X-rays in untreated myeloma patients. Ratios between bone resorption and bone formation markers added no further information on bone disease or survival. Only ICTP had prognostic value with an inverse correlation between serum levels and survival.

Aged↗
PubMed1999

Gender differences in the effects of long term growth hormone (GH) treatment on bone in adults with GH deficiency.

We recently observed that among patients with GH deficiency due to adult-onset hypopituitarism, men responded with a greater increase in serum levels of insulin-like growth factor I (IGF-I) and biochemical markers of bone metabolism than women when the same dose of recombinant human GH (rhGH) per body surface area was administered for 9 months. In the present study, 33 of the 36 patients in the previous trial (20 men and 13 women) continued therapy for up to 45 months. The dose of rhGH was adjusted according to side-effects and to maintain serum IGF-I within the physiological range. This resulted in a significant dose reduction in the men; consequently, the women received twice as much rhGH as the men (mean +/- SD, 1.9 +/- 1.1 vs. 1.0 +/- 0.6 U/day; P < 0.01). The increases in serum IGF-I levels and serum biochemical markers of bone metabolism were similar in men and women with these doses. The total bone mineral content (BMC) was increased after 33 and 45 months of treatment up to 5.1% (P = 0.004 and 0.0001). Bone mineral density (BMD), BMC, and the area of the femoral neck and the lumbar spine were also significantly increased after 33 and 45 months of treatment. When analyzed by gender, total body BMC, femoral neck BMD and BMC, and spinal BMC were significantly increased in males, but not in females (P < 0.05-0.01). In conclusion, rhGH treatment continued to have an effect on bone metabolism and bone mass for up to 45 months of therapy. The changes in bone mass were greater in the men, although they received lower doses of rhGH than the women. The results indicate that the sensitivity to GH in adult patients with GH deficiency is gender dependent.

Adult↗
PubMed1999

Smoking, antioxidant vitamins, and the risk of hip fracture.

Smoking increases the concentrations of free radicals, which have been suggested to be involved in bone resorption. We examined whether the dietary intake of antioxidant vitamins may modify the increased hip fracture risk associated with smoking. We prospectively studied 66,651 women who were 40-76 years of age. Forty-four of the cohort members who sustained a first hip fracture within 2-64 months of follow-up (n = 247) and 93 out of 873 age-matched controls were current smokers. Information on diet was obtained by a validated food-frequency questionnaire. The relative risk of hip fracture for current versus never smokers was analyzed in relation to the dietary intake of antioxidant vitamins stratified into two categories (low/high), where median intakes among the controls were used as cut-off points. After adjustment for major osteoporosis risk factors, the odds ratio (OR) for hip fracture among current smokers with a low intake of vitamin E was 3.0 (95% confidence interval 1.6-5.4) and of vitamin C 3.0 (1.6-5.6). In contrast, the OR decreased to 1.1 (0.5-2.4) and 1.4 (0.7-3.0) with high intakes of vitamin E and C, respectively. This effect was not seen for beta-carotene, selenium, calcium, or vitamin B6. In current smokers with a low intake of both vitamins E and C, the OR increased to 4.9 (2.2-11.0). The influence of the intake of these two antioxidant vitamins on hip fracture risk was less pronounced in former smokers. Our results suggest a role for oxidant stress in the adverse effects on the skeleton of smoking, and that an insufficient dietary intake of vitamin E and C may substantially increase the risk of hip fracture in current smokers, whereas a more adequate intake seems to be protective.

Adult↗
PubMed1999

Three isolation techniques for primary culture of human osteoblast-like cells: a comparison.

The culture of osteoblast-like cells of human origin has become an important experimental model in bone biology. We report here a comparison and evaluation of three of the most widely used systems available today: bone marrow stroma cell cultures (BMSC), human osteoblast explant cultures (hOB) and osteoblast explant cultures from collagenase-treated bone (hOBcol). Cultures from 16 bone specimens obtained from various donors were established and their expression of the osteoblast phenotype were then compared in secondary cultures by use of biochemical markers. BMSC had the highest basal and 1,25-dihydroxyvitaminD3 (1,25(OH)2D3)-induced alkaline phosphatase activities in all cell isolations, with levels approximately twice those in explant cultures. Basal osteocalcin secretion was low-to-undetectable in all cell cultures but was detected in 1,25(OH)2D3-stimulated cultures. BMSC produced half of the amount of osteocalcin synthesized in explant cultures. The BMSC cultures also synthesized the lowest amounts of type I collagen, whereas collagen type III synthesis did not differ significantly among the various cultures. When secondary cultures were treated with 100 nM dexamethasone in the presence of ascorbic acid (50 microg/mL) and beta-glycerophosphate (10 mM), cultures deposited calcium mineral into the cell layer within 2-4 weeks. PTH-induced cAMP formation was detected in only 5 of 15 isolations and no consistent isolation-dependent response pattern was seen. We conclude that BMSC cultures differ significantly from explant cultures obtained from the same bone specimen. However, all cultures represent cells which can differentiate further and induce mineralization of the extracellular matrix in response to osteoinductive drugs.

Adolescent↗
PubMed1999

Thrombin, but not bradykinin, stimulates proliferation in isolated human osteoblasts, via a mechanism not dependent on endogenous prostaglandin formation.

Osteolysis or osteosclerosis often occurs in bone tissue adjacent to chronic inflammatory processes. Numerous cytokines and inflammatory mediators have been implicated as osteoclast-activating agents, explaining inflammation-induced bone resorption. In many cases, the cause of the sclerosis seen in these lesions is less thoroughly investigated. We have studied the effects of thrombin and bradykinin, 2 inflammatory mediators, on the rate of proliferation in isolated human osteoblasts (hOBs). Thrombin, at and above 1 U/mL, stimulated the rate of thymidine incorporation into hOBs. The absolute cell number also increased, as measured by an assay based on the detection of cell metabolism. A synthetic peptide ligand for the thrombin receptor enhanced the rate of [3H]thymidine incorporation in hOBs, indicating that thrombin-induced proliferation is mediated via the tetheric thrombin receptor. The thrombin-induced proliferation was not affected by indomethacin, excluding prostanoids as mediators of this effect. Bradykinin did not affect either the rate of thymidine incorporation, or number of cells in long-term cultures of hOBs. In conclusion, the inflammatory mediator, thrombin, stimulates proliferation in isolated human osteoblasts probably via the recently described G-protein-coupled tetheric thrombin receptor. Thrombin may therefore be involved as a mediator of inflammation-induced sclerosis and bone formation.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1998

Excessive dietary intake of vitamin A is associated with reduced bone mineral density and increased risk for hip fracture.

BACKGROUND: The highest incidence of osteoporotic fractures is found in northern Europe, where dietary intake of vitamin A (retinol) is unusually high. In animals, the most common adverse effect of toxic doses of retinol is spontaneous fracture. OBJECTIVE: To investigate whether excessive dietary intake of vitamin A is associated with decreased bone mineral density and increased risk for hip fracture. DESIGN: A cross-sectional study and a nested case-control study. SETTING: Two counties in central Sweden. PARTICIPANTS: For the cross-sectional study, 175 women 28 to 74 years of age were randomly selected. For the nested case-control study, 247 women who had a first hip fracture within 2 to 64 months after enrollment and 873 age-matched controls were selected from a mammography study cohort of 66,651 women 40 to 76 years of age. MEASUREMENTS: Retinol intake was estimated from dietary records and a food-frequency questionnaire. Bone mineral density was measured with dual-energy x-ray absorptiometry. Hip fracture was identified by using hospital discharge records and was confirmed by record review. RESULTS: In multivariate analysis, retinol intake was negatively associated with bone mineral density. For every 1-mg increase in daily intake of retinol, risk for hip fracture increased by 68% (95% CI, 18% to 140%; P for trend, 0.006). For intake greater than 1.5 mg/d compared with intake less than 0.5 mg/d, bone mineral density was reduced by 10% at the femoral neck (P = 0.05), 14% at the lumbar spine (P = 0.001), and 6% for the total body (P = 0.009) and risk for hip fracture was doubled (odds ratio, 2.1 [CI, 1.1 to 4.0]). CONCLUSION: High dietary intake of retinol seems to be associated with osteoporosis.

Adult↗
PubMed1998

Population based case-control study of sick leave in postmenopausal women before diagnosis of hyperparathyroidism.

OBJECTIVE: To analyse sick leave in women at risk of primary hyperparathyroidism before its diagnosis. DESIGN: Case-control study nested within a screened cohort of postmenopausal women. Cases were women with hyperparathyroidism without prior knowledge of their disease and no traditional symptoms or complications. Controls were women from the screened population without hyperparathyroidism. SETTING: Population based screening within a Swedish community. SUBJECT: 48 case-control pairs of women aged 55-70 years. MAIN OUTCOME MEASURE: Sick leave during the 5 years before diagnosis. RESULTS: Total duration of sickness benefits was longer in the cases than controls, and this discrepancy included sick leave on full time or half time and for periods of longer than a week. Cases had an increased risk of sick leave more than half of the investigated time compared with controls (odds ratio 12). Doctors' certificates showed that the overrepresented sick leave in the cases related mainly to cardiovascular diseases. CONCLUSION: Asymptomatic mild primary hyperparathyroidism in postmenopausal women is accompanied by a previously unrecognised morbidity, which has consequences for clinical management of the disorder and its impact on the health economy.

Aged↗
PubMed1998

Tumor necrosis factor-alpha and -beta upregulate the levels of osteoprotegerin mRNA in human osteosarcoma MG-63 cells.

Osteoprotegerin (OPG) is a recently cloned soluble member of the tumor necrosis factor receptor family. OPG has been shown to inhibit osteoclast recruitment by binding to OPG-ligand, an osteoclast differentiating factor on osteoblastic stromal cells, thereby blocking osteoclastogenesis. In this report we have examined the effect of tumor necrosis factor-alpha (TNF-alpha) and tumor necrosis factor-beta (TNF-beta) on OPG mRNA levels in the human osteosarcoma cell line MG-63. We demonstrate that both TNF-alpha and TNF-beta dose- and time-dependently upregulate the mRNA levels of OPG. The effect is significant at and above 5 pM of TNF-alpha and 1 pM of TNF-beta. The stimulatory effect on OPG mRNA levels in MG-63 cells was detected after 2 hrs of incubation with TNF-alpha or TNF-beta. These data demonstrate that the expression of OPG in osteoblasts, with subsequent effects on osteoclastogenesis, is regulated by TNFs.

Bone Neoplasms↗
PubMed1998

Hormone replacement therapy and risk of hip fracture: population based case-control study. The Swedish Hip Fracture Study Group.

OBJECTIVE: To determine the relative risk of hip fracture associated with postmenopausal hormone replacement therapy including the effect of duration and recency of treatment, the addition of progestins, route of administration, and dose. DESIGN: Population based case-control study. SETTING: Six counties in Sweden. SUBJECTS: 1327 women aged 50-81 years with hip fracture and 3262 randomly selected controls. MAIN OUTCOME MEASURE: Use of hormone replacement therapy. RESULTS: Compared with women who had never used hormone replacement therapy, current users had an odds ratio of 0.35 (95 % confidence interval 0.24 to 0.53) for hip fracture and former users had an odds ratio of 0.76 (0.57 to 1.01). For every year of therapy, the overall risk decreased by 6% (3% to 9%): 4% (1% to 8%) for regimens without progestin and 11% (6% to 16%) for those with progestin. Last use between one and five years previously, with a duration of use more than five years, was associated with an odds ratio of 0.27 (0.08 to 0.94). After five years without hormone replacement therapy the protective effect was substantially diminished (-7% to 48%). With current use, an initiation of therapy nine or more years after the menopause gave equally strong reduction in risk for hip fracture as an earlier start. Oestrogen treatment with skin patches gave similar risk estimates as oral regimens. CONCLUSIONS: Recent use of hormone replacement therapy is required for optimum fracture protection, but therapy can be started several years after the menopause. The protective effect increases with duration of use, and an oestrogen-sparing effect is achieved when progestins are included in the regimen.

Administration, Cutaneous↗