Primary reconstruction of orbital fractures using patient-specific titanium milled implants: the Helsinki protocol.

Preoperative virtual planning and the use of patient-specific implants enable exact reconstruction of orbital fractures. We present our results and experience of reconstruction of isolated orbital fractures with patient-specific implants, according to the Helsinki protocol, in 15 patients who were followed up for at least three months postoperatively. The mean (range) difference between the positions of virtually planned, and postoperative, implants was 1.9 (0.5-5.6) mm. The postoperative volume of the fractured orbit was 1.34ml less than that of the non-fractured side, but this was not clinically relevant. None of the patients required reoperation and none had any implant-related complications during follow up. We conclude that patient-specific implants are an adaptable and reliable treatment for primary orbital trauma, and that the Helsinki protocol may have wider applications in the treatment of facial fractures.

Associations of dietary polyunsaturated fatty acids with bone mineral density in elderly women.

BACKGROUND/OBJECTIVES: Significance of dietary fatty acids on bone health is not clear, and the evidence is controversial. This study aimed to investigate the relationship between dietary polyunsaturated fatty acids (PUFAs) and bone mineral density (BMD) among elderly women. SUBJECTS/METHODS: Subjects (n=554) were drawn from the Kuopio OSTPRE Fracture Prevention Study. At baseline they filled a 3-day food record and a questionnaire on lifestyle factors, diseases and medications. BMD was measured at lumbar spine (L2-L4), femoral neck and total body by dual energy X-ray absorptiometry at baseline and after 3 years. The associations between dietary fatty acids and BMD were analyzed by a linear mixed model adjusting for potential dietary and non-dietary confounders. RESULTS: Our findings suggested a positive relationship between the dietary PUFAs and BMD at lumbar spine and in total body but not at femoral neck. Further analyses revealed that these results were due to associations among the women without hormone therapy (HT) at baseline. Among them, the intake of total PUFAs as well the intakes of linoleic and linolenic acids and total n-3 and n-6 fatty acids were significantly associated with BMD at lumbar spine; P for trend over the quartiles ranged between 0.013 and 0.001. Similarly, significant associations were demonstrated for total body BMD and fatty acids with an exception of total PUFA. No significant associations were found among women with HT at baseline. CONCLUSIONS: Our findings among elderly women without HT support the suggested beneficial effect of dietary PUFAs on bone health.

Bone health-related factors and the use of bisphosphonates in community setting--15-year follow-up study.

UNLABELLED: The present study investigated the bone health related factors that were associated with the use of bisphosphonates (BP) among 2,050 postmenopausal Finnish women. Low BMD + low trauma energy fracture was the strongest determinant of BP use, while other secondary causes of osteoporosis were less strongly related with BP use. BP use was associated with reduced femoral neck (FN) and lumbar spine (LS) bone loss rate. INTRODUCTION: The aim was to identify bone health related factors associated with the use of BP in a community setting. METHODS: A population-based sample of 2,050 Finnish postmenopausal women was measured with dual X-ray absorptiometry at the FN and LS in 1989, 1994, 1999 and 2004, and information on osteoporosis risk factors, including low-trauma energy fractures, were collected with postal inquiries. Self-reported use of BP in 2004 was considered as the end point variable. RESULTS: Among BP users, 12% had T-score > -2.0 SD and no fracture during follow-up (FU). In women without any bone medication, 26% had T-score < -2.0 SD or low-trauma energy fracture or both during the FU. In BP users, a significant reduction in FN and LS bone loss rate, cumulative with duration of use, was observed in ANCOVA (p < 0.001). Among BP users, there was a significantly higher proportion of women with several independent risk factors for osteoporosis and more spine and humerus fractures but less ankle fractures. T-score < -2 SD combined with low-trauma energy fracture was significantly related to the use of BPs (p < 0.001, OR = 15.96) and T-score < -2 SD was a stronger predictor of BP use (p < 0.001, OR = 13.29) than fracture (p > 0.05, OR = 1.35) in multivariate logistic regression. Other factors related with BP use were vitamin D use (p = 0.001, OR = 2.27), high number of medications (p < 0.001, OR = 1.26) and rheumatoid arthritis (p < 0.05, OR 2.55). CONCLUSIONS: These findings reveal the recent bone health-related indications for BP prescription.

Effect of calcium and vitamin D supplementation on bone mineral density in women aged 65-71 years: a 3-year randomized population-based trial (OSTPRE-FPS).

SUMMARY: The Osteoporosis Risk Factor and Prevention-Fracture Prevention Study (OSTPRE-FPS) was a randomized population-based open trial (n = 593). The supplementation group (n = 287) received daily cholecalciferol 800 IU + calcium 1,000 mg for 3 years while the control group (n = 306) received neither supplementation nor placebo. Daily vitamin D and calcium supplementation have a positive effect on the skeleton in ambulatory postmenopausal women. INTRODUCTION: vitamin D deficiency is common in the elderly, and vitamin D levels are associated with low bone mineral density (BMD). The working hypothesis was that vitamin D and calcium supplementation could prevent bone loss in ambulatory postmenopausal women. METHODS: the OSTPRE-FPS was a randomized population-based open trial with a 3-year follow-up in 3,432 women (aged 66 to 71 years). A randomly selected subsample of 593 subjects underwent BMD measurements. The supplementation group (n = 287) received daily cholecalciferol 800 IU + calcium 1,000 mg for 3 years while the control group (n = 306) received neither supplementation nor placebo. RESULTS: in the intention-to-treat analysis, total body BMD (n = 362) increased significantly more in the intervention group than in the control group (0.84% vs. 0.19%, p = 0.011). The BMD change differences at the lumbar spine (p = 0.372), femoral neck (p = 0.188), trochanter (p = 0.085), and total proximal femur (p = 0.070) were statistically nonsignificant. Analyses in compliant women (≥ 80% of use) resulted in stronger and statistically significant effects at the total body and femoral regions. CONCLUSION: daily vitamin D and calcium supplementation have a positive effect on the skeleton in ambulatory postmenopausal women with adequate nutritional calcium intake.

Effects of a low-frequency sound wave therapy programme on functional capacity, blood circulation and bone metabolism in frail old men and women.

OBJECTIVE: To evaluate the effects of a low-frequency sound wave therapy programme on functional capacity, blood circulation and bone metabolism of the frail elderly. DESIGN: Single-blind, randomized, controlled trial. SETTING: Two senior service centres. SUBJECTS: Forty-nine volunteers (14 males and 35 females) aged 62-93 years with up to 12 diagnosed diseases were allocated in either the intervention group (n = 30) or control group (n = 19). INTERVENTION: The intervention group underwent sound wave therapy, 3-5 times a week for 30 minutes per session over a period of 6 months. The control group received no intervention. MAIN MEASUREMENTS: Blood pressure, functional capacity, mobility, bone density, biochemical markers, isometric muscle strength, balance, and skin surface temperature. RESULTS: Compared with the control group, the intervention group's mobility and the amount of self-reported kilometres walked per week increased by 3 km (P<0.05), while levels of cholesterol (4.97 (0.72) to 4.52 (0.65) mmol/L, P =0.019), low-density lipoprotein (2.82 (0.72) to 2.45 (0.61) mmol/L, P =0.022), bone markers of total osteocalcin (11.0 (6.5) to 10.3 (5.9) ng/mL, P =0.048)) and tartrate-resistant acid phosphatase isoform 5b (2.50 (1.0) to 2.41 (1.1) IU/L, P =0.021)) decreased. The average skin surface temperature was significantly higher during active sessions at the end of the intervention than in the beginning (P = 0.004). No change was found during placebo sessions. CONCLUSIONS: Low-frequency sound wave therapy may have the potential to promote well-being of frail elderly subjects via improved functional capacity, especially in subjects who are too frail to undertake exercise.

Associations of vitamin D receptor, calcium-sensing receptor and parathyroid hormone gene polymorphisms with calcium homeostasis and peripheral bone density in adult Finns.

BACKGROUND: Thus far the search for osteoporosis candidate genes has focused less attention on the regulation of calcium homeostasis. Associations of vitamin D receptor (VDR) FokI, calcium-sensing receptor (CaSR) A986S and parathyroid hormone (PTH) BstBI polymorphisms with calcium homeostasis and peripheral bone density were investigated in adult Finns. METHODS: The subgroup of the population-based FINRISK survey consists of 339 healthy adults aged 31-43 years. Lifestyle data were assessed with questionnaires and food diaries. DNA was isolated from blood, and biochemical determinants of calcium metabolism were measured from blood and 24-hour urine samples. Bone mineral density (BMD) was measured using the DXA method at the distal forearm and by quantitative ultrasound (broadband ultrasound attenuation and speed of sound) at the calcaneus. Subjects were genotyped for VDR FokI, CaSR A986S and PTH BstBI polymorphisms. RESULTS: The CaSR 986S allele was associated with higher serum ionized calcium (p = 0.014). Forearm BMD was lowest for the PTH BstBI genotype bb in males (p = 0.023). VDR FokI and PTH BstBI polymorphisms showed a significant interaction on serum PTH (p = 0.010). The other gene-gene or diet-gene interactions studied showed no significant results. CONCLUSIONS: VDR, CaSR and PTH contribute to the genetic regulation of calcium homeostasis and peripheral bone density.

Selenium speciation and bioavailability in biofortified products using species-unspecific isotope dilution and reverse phase ion pairing-inductively coupled plasma-mass spectrometry.

In some regions of the world, where the bioavailability of selenium (Se) in soil is low and/or declining (e.g., due to use of high-sulfur fertilizers), there is increased risk of adverse affects on animals and human health. In recent years, increased research attention has focused on understanding the relationships between Se contents in foods and supplements and their nutritional benefits for animal and humans. The objective of this study was to use a species-unspecific isotope dilution and reverse phase ion pairing-inductively coupled plasma-mass spectrometry techniques for the identification and quantification of Se species in biofortified grains (i.e., wheat and triticale), flour, and wheat biscuits. The information on Se species was used to gain an understanding of the bioavailability of Se in biofortified and process-fortified wheat biscuits used in a clinical trail. The major Se species identified in biofortified and process-fortified samples were selenomethionine (76-85%) and selenomethionine selenoxide (51-60%), respectively. Total plasma Se concentrations in the biofortified Se exposure group were found to increase throughout the 6 month trial period (mean=122 microg L(-1) at 0 months to 194 microg L(-1) at 6 months). In contrast, the trial group exposed to process-fortified Se biscuits showed little increase in mean total Se plasma concentrations until 4 months of exposure (mean=122 microg L(-1) at 0 months to 140 microg L(-1) at 4 months) that remained constant until the end of the trial period (mean=140 microg L(-1) at 4 months to 138 microg L(-1) at 6 months). The difference in total Se plasma concentrations may be due to the presence and bioavailability of different Se species in biofortified and process-fortified biscuits. An understanding of Se speciation in foods enables better understanding of pathways and their potential benefits for animals and humans.

Association between functional capacity tests and fractures: an eight-year prospective population-based cohort study.

UNLABELLED: This study of postmenopausal women (n=2,928) with an eight-year follow-up revealed that impairment in functional status associated with the increased fracture risk. The standing-on-one-foot and grip strength tests and a question about self-assessed ability to move can be used to identify women with a high risk of suffering a fracture. INTRODUCTION: Poor functional status has pointed to associate with injurious falls and consequent fractures. Our aim was to define association between functional capacity and fractures. METHODS: This study was based on the Osteoporosis Risk Factor and Prevention Study (OSTPRE). A total of 2,928 postmenopausal women took part in the functional capacity and muscle strength tests. The duration of fracture follow-up varied from 6.43 to 9.86 (mean 8.37) years and the first fracture was the end-point event for the statistical analyses. All analyses were done with Cox-regression. RESULTS: A total of 261 end-point fractures occurred. In multivariate analysis the inability to stand-on-one-foot for 10 seconds increased the risk of hip fracture (hazard ratio with 95% CI) 9.11-fold (1.98-42.00). Decreased grip strength associated with 1.05-fold (1.01-1.09) increased risk of hip fractures. Low leg extension strength associated with 1.02-fold (1.00-1.03) higher risk for all fractures. The self-assessed ability to walk less than 100 meters at baseline increased the risk of ankle 2.36-fold (1.10-5.08), hip 11.57-fold (2.73-49.15) and clinical vertebral fractures 3.85-fold (1.45-10.22). CONCLUSION: According to these results the standing-on-one-foot less than 10 seconds, grip strength and a question about ability to walk less than 100 meters may help to predict postmenopausal fractures.

Acute effects of different phosphorus sources on calcium and bone metabolism in young women: a whole-foods approach.

The recommended dietary phosphorus intake is exceeded in the typical Western diet. However, few studies have been conducted on the bioavailability and metabolic consequences of dietary phosphorus from different food sources. In this study, acute effects of dietary phosphorus from three different food sources and a phosphate supplement on calcium and bone metabolism were investigated. Sixteen healthy women aged 20-30 years were randomized to five controlled 24-hour study sessions, each subject serving as her own control. At the control session, calcium intake was ca. 250 mg and phosphorus intake ca. 500 mg. During the other four sessions, phosphorus intake was about 1,500 mg, 1,000 mg of which was obtained from meat, cheese, whole grains, or a phosphate supplement, respectively. The foods served were exactly the same during the phosphorus sessions and the control session; only phosphorus sources varied. Markers of calcium and bone metabolism were followed. Analysis of variance with repeated measures was used to compare the study sessions. Only the phosphate supplement increased serum parathyroid hormone (S-PTH) concentration compared with the control session (P = 0.031). Relative to the control session, meat increased markers of both bone formation (P = 0.045) and bone resorption (P = 0.049). Cheese decreased S-PTH (P = 0.0001) and bone resorption (P = 0.008). These data suggest that the metabolic response was different for different foods.

Safety aspects and cholesterol-lowering efficacy of low fat dairy products containing plant sterols.

OBJECTIVE: The aim of this study was to investigate whether a plant sterol mixture would reduce serum cholesterol when added to low fat dairy products in subjects with hypercholesterolaemia, and to examine the effects of the mixture on the serum plant sterol and fat-soluble vitamin levels. DESIGN: A parallel, double-blind study. SETTING: The study was performed in three different locations in Finland. SUBJECTS: In total, 164 mildly or moderately hypercholesterolaemic subjects participated in the study. METHODS: The subjects were randomly divided into two groups: a plant sterol group and a control group. The subjects consumed the products for 6 weeks after a 3-week run-in period. The targeted plant sterol intake was 2 g/day in the sterol group. RESULTS: During the treatment period, there was a 6.5% reduction in serum total cholesterol in the sterol group while no change was observed in the control group (P<0.0005). Serum low-density lipoprotein (LDL) cholesterol was reduced by 10.4% in the sterol group and by 0.6% in the control group (P<0.00005). There was no change during the trial in serum high-density lipoprotein (HDL) cholesterol or triacylglycerol concentrations. The HDL/LDL cholesterol ratio increased by 16.1% in the sterol group and by 4.3% in the control group (P=0.0001). Serum plant sterol levels increased significantly (P=0.0001) in the sterol group. None of the fat-soluble vitamin levels decreased significantly when changes in serum total cholesterol were taken into account. The hypocholesterolaemic effect of sterol administration was not influenced by apolipoprotein E phenotype. CONCLUSIONS: Yoghurt, low-fat hard cheese and low-fat fresh cheese enriched with a plant sterol mixture reduced serum cholesterol in hypercholesterolaemic subjects and no adverse effects were noted in the dietary control of hypercholesterolaemia.

Teenage girls and elderly women living in northern Europe have low winter vitamin D status.

OBJECTIVE: To determine the vitamin D status (serum 25-hydroxyvitamin D; S-25OHD) in adolescent girls and elderly community-dwelling women living in four countries of northern Europe and to explain differences in S-25OHD concentrations between and within the countries. DESIGN: A cross-sectional observational study conducted in a standardised way during February-March. S-25OHD was analysed by high-performance liquid chromatography. Vitamin D and calcium intake was calculated using a standardised food composition database. SETTING: Denmark, Finland, Ireland, and Poland. SUBJECTS: A total of 199 girls (mean (s.d.) age 12.6 (0.5) y) and 221 women (mean (s.d.) age 71.8 (1.4) y). RESULTS: The median (inter quartiles) concentration of S-25OHD was 29.4 (20.3, 38.3) nmol/l for the girls and 40.7 (28.0, 54.2) nmol/l for the women. S-25OHD below 25 nmol/l was found in 37% of the girls and 17% of the women, and S-25OHD below 50 nmol/l was found in 92% of the girls and 37% of the women. Positive significant determinants for S-25OHD in girls were use of vitamin D supplements, and in women sun habits, dietary vitamin D intake, use of vitamin D and calcium supplements. Body mass index and smoking were negative determinants in women. For women predictors could explain the differences between countries (P(country) = 0.09, R(2) = 0.39), but for girls the difference remained significant even after including predictors (P(country) = 0.03, R(2) = 0.15). CONCLUSION: Vitamin D status is low in northern Europe during winter. More than one-third of the adolescent girls have vitamin D status below 25 nmol/l and almost all are below 50 nmol/l. Two-thirds of the elderly community-dwelling women have vitamin D status below 50 nmol/l. Use of vitamin D supplements is a significant positive determinant for S-25OHD for both girls and women (P = 0.001). SPONSORSHIP: The European Fifth Framework Programme (Contract No. QLK1-CT-2000-00623).

A 7-week reduction in salt intake does not contribute to markers of bone metabolism in young healthy subjects.

BACKGROUND: Sodium intake increases urinary calcium excretion and may thus lead to negative calcium balance and bone loss. OBJECTIVE: We hypothesised that reducing sodium intake would reduce urinary calcium excretion and have a beneficial influence in bone metabolism. DESIGN: A total of 29 subjects, 14 males and 15 females, were divided into two study groups. One group (low-sodium group (LS)) reduced sodium intake for 7 weeks by substituting low-salt alternatives for the most important dietary sources of sodium. The other group, serving as a control group (C), was given the same food items in the form of normally salted alternatives. Fasting serum samples as well as 24-h urine samples were obtained in the beginning and at the end of the study. Urinary sodium, urinary calcium, urinary creatinine, serum calcium, serum phosphate, serum creatinine, serum parathyroid hormone (s-PTH), serum C-terminal telopeptides of Type-I collagen and serum bone alkaline phosphatase (s-B-ALP) were analysed. RESULTS: The LS group showed a significant decline (P = 0.001) in urinary sodium/creatinine ratio without a significant effect on urinary calcium/creatinine ratio. In the LS group, s-PTH increased (P = 0.03). The C group showed an increase in s-PTH (P = 0.05) and in s-B-ALP, but no differences were observed between the study groups in the changes of serum markers of calcium and bone metabolism. CONCLUSIONS: We have shown that reducing the sodium intake of young, healthy people with adequate calcium intake over a 7-week period does not affect the markers of bone metabolism.

Numerical study of wave propagation in uniaxially anisotropic Lorentzian backward-wave slabs.

The propagation and refraction of a cylindrical wave created by a line current through a slab of backward-wave medium, also called left-handed medium, is numerically studied with a finite-difference time-domain method. The slab is assumed to be uniaxially anisotropic. Several sets of constitutive parameters are considered and comparisons with theoretical results are made. Electric field distributions are studied inside and behind the slab. It is found that the shape of the wave fronts and the regions of real and complex wave vectors are in agreement with theoretical results.

Dietary calcium intake in premenopausal Bangladeshi women: do socio-economic or physiological factors play a role?

OBJECTIVE: Evaluation of data on dietary calcium intake in premenopausal women of two socio-economic groups in Bangladesh. DESIGN: A cross sectional study. Three days dietary records were used to estimate habitual calcium intake. SETTING: Two regions of Bangladesh. The Dhaka city area and the Betagair Union in the sub-district Nandail, Mymensingh. SUBJECTS: A total of 191 subjects of two groups (low socio-economic group=group L, n=101 and high socio-economic group=group H, n=90) of Bangladeshi women aged 16-40 y. About 87% of the subjects were housewives and the rest 13% were distributed in other different professions. Each group consisted of three sub-groups (non-pregnant non-lactating=1, pregnant=2 and lactating=3). RESULTS: : The influence of socio-economic status on dietary intake of calcium (P<0.001) was observed in this study. The dietary intake of calcium was influenced by physiological status (PS) in high income group only (P<0.005). The mean dietary calcium intake was significantly higher (P&<0.005) in all sub-groups of this group compared with the corresponding sub-groups in low income group. Although in group H, 47% of subjects failed to meet even the lowest level (400-500 mg/day) of WHO recommended dietary allowances (RDA) of calcium for adult women. No subject in group L was found to meet the RDA level. Moreover, 63% of the women in group L had calcium intake lower than 200 mg/day. These figure could be more critical in both groups if we consider the recent USA-RDAs of calcium for adult women (1000 mg/day). The observed sources of dietary calcium were different in the two groups. CONCLUSIONS: The results of the study suggested that low calcium intake could reduce the bone accretion rates and increase the risk of osteoporosis in the subjects of the present study. Calcium rich food may be recommended for women in both groups.

Vitamin D deficiency: a concern in premenopausal Bangladeshi women of two socio-economic groups in rural and urban region.

OBJECTIVE: The study was designed to evaluate the vitamin D status in women of different physiological status of two socio-economic groups in Bangladesh. DESIGN: A cross-sectional study, using serum 25-hydroxyvitamin D (25-OHD), calcium, phosphorus and alkaline phosphatase activity. SETTING: Two regions of Bangladesh. The Dhaka city area and west region of Nandail (Betagair Union), Mymensingh. SUBJECTS: Representative subjects of two groups (low socio-economic group=group L, n=99; and high socio-economic group=group H, n=90) of Bangladeshi women aged 16-40 y. About 87% of the subjects were housewives and the rest, 13%, were distributed among other different professions. Each group comprised of three sub-groups (non-pregnant non-lactating=1, pregnant=2, and lactating=3). RESULTS: The influence of socio-economic status and physiological status on serum 25-OHD concentration (P=0.038, P=0.015, respectively), serum calcium concentration (P<0.001, P<0.001, respectively) and alkaline phosphatase activity (P<0.001, P<0.001, respectively) were observed. The distribution of serum 25-OHD concentration in both groups was shifted overall toward the lower limit of the normal range. Seventeen percent of women in group L and 12% of women in group H had serum 25-OHD concentration <25 nmol/l. Hypovitaminosis D (serum 25-OHD concentration < or = 37.5 nmol/l) was observed in 50% of subjects in group L and 38% of subjects in group H, respectively. The prevalence of hypovitaminosis was higher in lactating subjects of the groups L and H (63 and 46%, respectively) than in the other sub-groups in the same group. CONCLUSIONS: The results of the study suggested that women in Bangladesh were at risk of hypovitaminosis D and lactation was an additional risk factor in low income groups. The situation may increase the risk of bone loss.

Vitamin D deficiency and bone health in healthy adults in Finland: could this be a concern in other parts of Europe?

A low vitamin D status could be a concern not only in children and the elderly in Europe, but also in adults. We do not know the effect of mild vitamin D deficiency on bone in this age group. The aim of this study was to detect the prevalence of low serum 25-hydroxyvitamin D [S-25(OH)D] and elevated serum intact parathyroid hormone (S-iPTH) concentrations in healthy young adults in the winter in northern Europe and to characterize the determinants of these variables. In addition, we studied the association between vitamin D status and forearm bone mineral density (BMD) in this population group. Three hundred and twenty-eight healthy adults (202 women and 126 men, 31-43 years) from southern Finland (60 degrees N) participated in this study conducted in February through March 1998. Fasting overnight blood samples were collected in the morning. Forearm BMD was measured by dual-energy X-ray absorptiometry (DXA). The mean daily vitamin D intake met the recommendations in the men (5.6 +/- 3.2 microg) and almost met it in the women (4.7 +/- 2.5 microg). The mean S-25(OH)D concentrations did not differ between genders (women, 47 +/- 34 nM; men, 45 +/- 35 nM; mean +/- SD), but the women had significantly higher mean S-iPTH levels than the men (women, 30 +/- 13 ng/liter; men, 24 +/- 12 ng/liter; p < 0.001). Low S-25(OH)D concentrations (<25 nM) were found in 26.2% of the women (53 women) and 28.6% of the men (36 men), respectively. Based on nonlinear regression analysis between S-25(OH)D and S-iPTH concentration, the S-iPTH concentration started to increase with S-25(OH)D concentrations lower than approximately 80 nM in the women and lower than approximately 40 nM in the men. Based on this relation between S-25(OH)D and S-iPTH concentrations, 86% of the women and 56% of the men had an insufficient vitamin D status. In linear regression analysis, the main positive determinants of S-25(OH)D were dietary vitamin D intake (p < 0.02), the use of supplements (p < 0.005), alcohol intake (p < 0.05), and age (p < 0.005). Smoking associated negatively with the S-25(OH)D concentration (p < 0.03). The main determinants of S-iPTH were S-25(OH)D (p < 0.01), dietary calcium intake (p < 0.02), and body mass index (BMI; p < 0.01). In addition, female gender was associated with higher S-iPTH concentration. The mean daily dietary calcium intake was 1,037 +/- 489 mg and 962 +/- 423 mg, in the men and women, respectively. Significantly lower forearm BMD was found in the men (p = 0.01) but not in the women (p = 0.14) with higher S-iPTH concentrations. Low vitamin D status was prevalent in these young adults in northern Europe in winter, although the vitamin D intake met the recommendation. This probably is not a local problem for northern Europe, because the natural sources of vitamin D are scarce and fortification is not very common in Europe, and with the exception of the southern part of Europe, sunshine is not very abundant in this part of the world. Thus, the results of this study indicate that more attention should be focused on vitamin D status and the sources of vitamin D in these countries.

Novel non-TGF-beta-binding splice variant of LTBP-4 in human cells and tissues provides means to decrease TGF-beta deposition.

Small latent TGF-beta consists of latency associated peptide (LAP) bound to the 25 kDa TGF-beta by noncovalent interactions. Small latent TGF-beta is secreted from cells and deposited into the extracellular matrix as covalent complexes with its binding proteins, LTBPs. Four LTBPs have been molecularly cloned and their structures contain repetitive sequences. The 3rd 8-Cys repeats of LTBP-1, -3 and -4 are able to associate with small latent TGF-beta. We analyzed by RT-PCR the expression of LTBPs 1-4 in a panel of cultured human cell lines including fibroblasts of different origin, endothelial cells and immortalized keratinocytes. LTBPs were expressed in an overlapping manner, but differences in their expression levels were detected. SV-40 transformed human embryonic lung fibroblasts contained less of the mRNAs for the LTBPs, suggesting that malignant transformation leads to decrease in LTBP expression. A novel alternatively spliced form of LTBP-4 lacking the 3rd 8-Cys repeat (LTBP-4delta8-Cys3rd) was identified. LTBP-4delta8-Cys3rd does not bind TGF-beta and it was found to be expressed in the same tissues as the full length LTBP-4. The exon-intron structure of LTBP-4 around the 3rd 8-Cys repeat was similar to those of LTBP-2 and -3. LTBP-4delta8-Cys3rd was produced by alternative splicing over two exons. In addition, HL-60 promyelocytic leukemia cells expressed a splice variant lacking only one exon of this region. The expression of the non-TGF-beta-binding variant of LTBP-4 may be important for the regulation of TGF-beta deposition in tissues. Since LTBPs are a part of the extracellular matrix microfibrils, the LTBP-4delta8-Cys3rd protein may also be involved in various structural functions not related to TGF-beta signaling.

A model for gene therapy of human hereditary lymphedema.

Primary human lymphedema (Milroy's disease), characterized by a chronic and disfiguring swelling of the extremities, is associated with heterozygous inactivating missense mutations of the gene encoding vascular endothelial growth factor C/D receptor (VEGFR-3). Here, we describe a mouse model and a possible treatment for primary lymphedema. Like the human patients, the lymphedema (Chy) mice have an inactivating Vegfr3 mutation in their germ line, and swelling of the limbs because of hypoplastic cutaneous, but not visceral, lymphatic vessels. Neuropilin (NRP)-2 bound VEGF-C and was expressed in the visceral, but not in the cutaneous, lymphatic endothelia, suggesting that it may participate in the pathogenesis of lymphedema. By using virus-mediated VEGF-C gene therapy, we were able to generate functional lymphatic vessels in the lymphedema mice. Our results suggest that growth factor gene therapy is applicable to human lymphedema and provide a paradigm for other diseases associated with mutant receptors.

Does it make a difference how and when you take your calcium? The acute effects of calcium on calcium and bone metabolism.

BACKGROUND: Calcium supplements are widely used to prevent osteoporosis. However, little is known about the metabolic effects of different dosages and of the timing of the dosages. OBJECTIVE: The aim was to study the effects of the timing of the dose (study 1), the effects of the size of the dose (study 2), and the effects of small repetitive doses (study 3) of calcium on calcium and bone metabolism in women. DESIGN: The investigation was conducted in 3 parts, each with 10 participants. In study 1, calcium loads (0 and 25 mg/kg body wt) were taken at 0900 and 2100. In study 2, calcium loads of 0, 250, and 1000 mg were taken at 0900. In study 3, calcium loads of 0 and 200 mg were taken 4 times/d. Markers of calcium and bone metabolism were followed. RESULTS: There was no significant difference in the response of serum parathyroid hormone (PTH) to the calcium load taken at 0900 and that at 2100. There was a significant dose-response effect of the calcium load on serum ionized calcium (P = 0.00005) and serum PTH (P = 0.0003). Small calcium doses (200 mg) taken 4 times/d kept the PTH secretion at a lower level than during the control day (P = 0.016). None of the doses caused significant changes in the markers of bone formation and resorption measured. CONCLUSIONS: The calcium loads had no significant effect on the markers of bone formation and resorption measured, although even small calcium doses decreased serum PTH and increased serum ionized calcium concentrations rapidly. The effect was similar whether calcium was taken in the morning or in the evening.

Vitamin D status affects serum parathyroid hormone concentrations during winter in female adolescents: associations with forearm bone mineral density.

BACKGROUND: Vitamin D deficiency leads to secondary hyperparathyroidism, which has a negative effect on bone metabolism in the elderly. Puberty is an important time of bone metabolism and growth. The effect of serum 25-hydroxyvitamin D [25(OH)D] concentrations on parathyroid hormone concentrations and bone mineral density (BMD) has not been well studied cross-sectionally in adolescents. OBJECTIVE: We studied the effect of vitamin D status on serum intact parathyroid hormone (iPTH) concentrations and bone metabolism in adolescents. DESIGN: One hundred seventy-eight healthy female adolescents (aged 14-16 y) volunteered for this study, which was conducted in Finland (Helsinki, 60 degrees N) during the winter. Forearm BMD at radial and ulnar sites was measured by dual energy X-ray absorptiometry. The determinants of different variables were studied by use of regression models. RESULTS: On the basis of the relation between serum 25(OH)D and iPTH concentrations, serum 25(OH)D concentrations > approximately 40 nmol/L were needed to keep serum iPTH concentrations low. One hundred ten subjects (61.8%) had serum 25(OH)D concentrations < or =40 nmol/L. Twenty-four subjects (13.5%) were considered vitamin D deficient when the serum 25(OH)D concentration of 25 nmol/L was used as a cutoff. Subjects with serum 25(OH)D concentrations < or =40 nmol/L had low mean forearm BMD values at both the radial (P = 0.04) and ulnar (P = 0.08) sites. CONCLUSION: A large percentage of adolescent females have low vitamin D status during the winter in Finland, which seems to have negative effects on bone health.