Lactose malabsorption and intolerance and peak bone mass

BACKGROUND & AIMS: Lactose malabsorption per se is not associated with alterations of bone mineral density (BMD) or calcium intake, but when intolerance symptoms are present a lower calcium intake and reduction of BMD values are evident. The purpose of this study was to evaluate whether lactose intolerance interferes with the achievement of an adequate peak bone mass in young adults. METHODS: Of 103 enrolled healthy subjects, 55 proved to be lactose malabsorbers with H(2) breath test after lactose administration, and 29 of them experienced intolerance symptoms (diarrhea, abdominal pain, bloating, flatulence). Lumbar and femoral BMD by dual-energy X-ray absorptiometry was measured, and calcium intake and biochemical indices of bone and mineral metabolism were evaluated. RESULTS: Lumbar and femoral BMD, calcium intake, and mineral metabolism did not differ between malabsorbers and absorbers, although among malabsorbers, intolerant subjects showed significant alterations of all these parameters in comparison with tolerant subjects. A strict correlation was evident between BMD values and both severity of symptoms and calcium intake and between calcium intake and severity of symptoms. CONCLUSIONS: Lactose intolerance prevents the achievement of an adequate peak bone mass and may, therefore, predispose to severe osteoporosis.     

Lactose malabsorption and intolerance in the elderly.

BACKGROUND: Lactase activity declines with age in rats, but it is not clear whether this model is also shared by humans. Few studies have evaluated lactose intolerance and malabsorption in the elderly and no definite conclusions can be drawn. The aim of our study was therefore to verify the impact of age on lactose intolerance and malabsorption. METHODS: Eighty-four healthy subjects took part in the study. Thirty-three were <65 years, 17 were between 65 and 74 years and 34 were >74 years. All the subjects underwent a preliminary evaluation of intestinal gas production capacity and oro-cecal transit time by H2/CH4 breath test after lactulose. After a 3-day period, an H2/CH4 breath test after lactose was performed. The occurrence of intolerance symptoms during the test and in the 24 h after the test was recorded. RESULTS: Breath H2 and CH4 excretion parameters at fasting and after lactulose did not differ between the three groups. Cumulative breath H2 excretion after lactose was higher in subjects >74 years than in subjects <65 years and in subjects aged 65-74 years, while no difference was found between the latter two groups. In subjects >74 years, the prevalence of lactose malabsorption was higher than in the other two groups, while no significant difference was observed between subjects <65 years and subjects aged 65-74 years. Within the malabsorber subjects, the prevalence of lactose intolerance was higher in subjects <65 years than in those aged 65-74 years and in those aged >74 years. No significant difference was found between the latter two groups. No difference was found between the three groups in terms of daily calcium intake and a significant negative correlation between symptom score and daily calcium intake was only found in the group of subjects aged <65 years. CONCLUSIONS: As age increases, the prevalence of lactose malabsorption shows an increase while the prevalence of intolerance symptoms among malabsorbers shows a decrease. Accordingly, daily calcium intake was similar among the adults and elderly studied.     

Relationships between bone mineral density, serum vitamin D metabolites and calcium:phosphorus intake in healthy perimenopausal women

OBJECTIVES: To determine the relationships between serum vitamin D metabolites, bone mass, and dietary calcium and phosphorus in a cohort of 510 healthy Danish perimenopausal women. DESIGN: A population-based cross-sectional study. SUBJECTS: A total of 510 healthy women aged 45-58 years, with amenorrhoea for 3-24 months. None of the women was using hormone replacement therapy. MEASUREMENTS: Measurements of total bone mineral content and regional bone mineral density were performed by dual-energy X-ray absorptiometry. Analyses of serum levels of 25-OHD and 1,25-(OH)2D, intact PTH, ionized calcium and phosphate, as well as biochemical markers of bone turnover in blood and urine. Assessment of calcium and phosphorus intake using dietary records. RESULTS: A consistent inverse relationship between serum 1,25-(OH)2D and bone mineral content/ density was found in whole-body mineral content (P = 0.001), spine (P = 0.005) and femoral neck (P<0.05). There was a positive relationship between levels of 1,25-(OH)2D and biochemical bone markers, indicating that high levels of 1,25-(OH)2D are accompanied by increased bone turnover. The dietary calcium:phosphorus ratio was inversely related to serum 1,25-(OH)2D (P = 0.04) and positively related to bone mineral density (P<0.0005). No relationships could be detected between levels of PTH, serum ionized calcium and phosphate, and serum vitamin D metabolites. CONCLUSION: Within normal physiological range, elevated levels of 1,25-(OH)2D were associated with decreased bone mineral density and content, reduced calcium:phosphorus ratio in the diet and increased bone turnover.     

Lactose Malabsorption and Intolerance in the Elderly

Background: Lactase activity declines with age in rats, but it is not clear whether this model is also shared by humans. Few studies have evaluated lactose intolerance and malabsorption in the elderly and no definite conclusions can be drawn. The aim of our study was therefore to verify the impact of age on lactose intolerance and malabsorption. Methods: Eighty-four healthy subjects took part in the study. Thirty-three were < 65 years, 17 were between 65 and 74 years and 34 were > 74 years. All the subjects underwent a preliminary evaluation of intestinal gas production capacity and oro-cecal transit time by H 2 /CH 4 breath test after lactulose. After a 3-day period, an H 2 /CH 4 breath test after lactose was performed. The occurrence of intolerance symptoms during the test and in the 24 h after the test was recorded. Results: Breath H 2 and CH 4 excretion parameters at fasting and after lactulose did not differ between the three groups. Cumulative breath H 2 excretion after lactose was higher in subjects > 74 years than in subjects < 65 years and in subjects aged 65-74 years, while no difference was found between the latter two groups. In subjects > 74 years, the prevalence of lactose malabsorption was higher than in the other two groups, while no significant difference was observed between subjects < 65 years and subjects aged 65-74 years. Within the malabsorber subjects, the prevalence of lactose intolerance was higher in subjects < 65 years than in those aged 65-74 years and in those aged > 74 years. No significant difference was found between the latter two groups. No difference was found between the three groups in terms of daily calcium intake and a significant negative correlation between symptom score and daily calcium intake was only found in the group of subjects aged < 65 years. Conclusions: As age increases, the prevalence of lactose malabsorption shows an increase while the prevalence of intolerance symptoms among malabsorbers shows a decrease. Accordingly, daily calcium intake was similar among the adults and elderly studied.     

Fracture thresholds in osteoporosis: implications for hormone replacement treatment.

The bone mineral densities of the lumbar spine and femoral neck were determined by dual energy chi ray absorptiometry in 110 women aged 40-82 years (average 65 years) with spinal osteoporosis who had had at least one atraumatic vertebral compression fracture and in 1026 normal women aged 40-79 years (average 52 years). The women with osteoporosis showed a significant decrease in bone mineral density (BMD) at the lumbar spine and femoral neck compared with age matched normal women (sixth decade of life -26% spine, -23% femoral neck; seventh decade -26% spine, -16% femoral neck). The fracture threshold, defined as the 90th centile of spinal BMD for women with osteoporosis, was 0.81 g/cm2 at the lumbar spine and 0.656 g/cm2 at the femoral neck. Five per cent of normal women aged 40-49 years, 20% aged 50-59 years, and 45% aged 60-69 years had a BMD below this threshold. To maintain the bones of women above the fracture threshold until the age of 70 years about 50% of postmenopausal women need hormone replacement therapy. However, if the BMD is to be kept above the fracture threshold for a women's lifetime, e.g. until the age of 80-90 years, then most women will need treatment, though for various lengths of time depending on their initial BMD. Measurements of BMD in postmenopausal women currently help in identifying the risk of osteoporotic fractures but in the lifetime assessment of risk in a single subject they may have a more important role in deciding the duration of hormone replacement therapy.     

Lactose and calcium absorption in postmenopausal osteoporosis

The prevalence of lactase deficiency and the relationship between lactose and calcium malabsorption in postmenopausal osteoporosis has been assessed in 46 subjects. Malabsorption of lactose occurred in 25 (54%) of the subjects and was associated with a significantly lower milk intake. Malabsorption of calcium occurred in 11 (44%) of the lactase-deficient subjects and in 11 (52%) of normal lactose absorbers. There was no relationship between lactose and calcium malabsorption. Vertebral and forearm mineral densities were not significantly different between normal lactose absorbers and lactase-deficient subjects.     

Low bone density is an etiologic factor for stress fractures in athletes

OBJECTIVE: To determine whether low bone density and other risk factors for osteoporosis are associated with stress fractures in athletes. DESIGN: Case-control study. SETTING: Institutional sports injury clinic with primary and secondary care. PARTICIPANTS: Twenty-five athletes (nineteen women) with scintigraphically confirmed stress fractures matched for sex, age, weight, height, and exercise history with 25 control athletes with no history of bone injury. MEASUREMENTS AND MAIN RESULTS: Bone mineral density measured by dual-energy x-ray absorptiometry was significantly lower in athletes with fractures than in control athletes: In the spine, bone mineral density was 1.01 +/- 0.14 g/cm2 in athletes with fractures and 1.11 +/- 0.13 g/cm2 in control athletes (P = 0.02). In the femoral neck, it was 0.84 +/- 0.09 g/cm2 in athletes with fractures and 0.90 +/- 0.11 g/cm2 in control athletes (P = 0.005). It was also significantly lower in the Ward triangle (P = 0.01) and the greater trochanter (P = 0.01). Eight athletes with fractures and no control athletes had less than 90% of predicted age-related spine density (P = 0.01), and three athletes with fractures had bone mineral densities that were 2 SDs or more below this predicted level. More athletes with fractures than control athletes had current menstrual irregularity (amenorrhea or oligomenorrhea) (P less than 0.005). Fewer athletes with fractures were using oral contraceptives (P less than 0.05). Seven-day diet records indicated similar energy and nutrient intakes, except athletes with fractures had lower calcium intakes (697 +/- 242 mg/d compared with 832 +/- 309 mg/d; P = 0.02). Dairy product intake was lower in athletes with fractures since leaving high school (P less than 0.05). The incidence of a family history of osteoporosis was similar in both groups. CONCLUSIONS: In athletes with similar training habits, those with stress fractures are more likely to have lower bone density, lower dietary calcium intake, current menstrual irregularity, and lower oral contraceptive use.     

Sustained-release sodium fluoride in the treatment of the elderly with established osteoporosis

BACKGROUND: We ascertained the safety and efficacy of fluoride in augmenting spinal bone mass and reducing spinal fractures in older women with established osteoporosis. We compared a combination of sustained-release sodium fluoride, calcium citrate, and cholecalciferol (SR-NaF group) with calcium and cholecalciferol alone (control group). METHODS: Eighty-five ambulatory women aged 65 years or older with 1 or more nontraumatic vertebral compression fractures were enrolled in a 42-month randomized, double-blind, placebo-controlled trial. Primary outcome measures were vertebral fracture rate, bone mass, and safety. RESULTS: The vertebral fracture rate determined by means of computer assistance in the SR-NaF group was significantly lower than that in the control group (relative risk [RR], 0.32; 95% confidence interval [CI], 0.14-0.73; P =.007). Results of visual adjudicated inspection also confirmed a significant reduction in fracture rate (RR, 0.40; 95% CI, 0.17-0.95; P =.04). Bone mineral density in L2 through L4 increased significantly from baseline in the SR-NaF group by 5.4% (95% CI, 2.7%-8.2%; P<.001), and by 3.2% in the control group (95% CI, 0.8%-5.6%; P =.01). The between-group differences in bone mineral density were not significant. The femoral neck and total hip bone mineral density remained stable in the SR-NaF group and was not significantly different from that of the control group. There were no significant differences in adverse effects between groups. CONCLUSION: The SR-NaF group significantly decreased the risk for vertebral fractures and increased spinal bone mass without reducing bone mass at the femoral neck and total hip.     

Vertebral morphometry by X-ray absorptiometry before and after liver transplant: a cross-sectional study.

OBJECTIVES: To evaluate bone density and fracture prevalence in patients with end-stage liver diseases (ESLD) awaiting liver transplant and in orthotopic liver-transplant (OLTx) recipients by using dual energy X-ray absorptiometry. DESIGN: In a cross-sectional study 27 patients (16 males and 11 females, mean age 49.9 +/- 1.7 years) with ESLD, and 36 subjects (26 males and 10 females, mean age 50.5 +/- 1.6 years) who had undergone OLTx 1-70 months before, were recruited. METHODS: All patients underwent biochemical assessment of mineral metabolism. Bone density measurement of the spine and femur and morphometric X-ray absorptiometry (MXA) of the vertebrae were also obtained. RESULTS: Bone density was decreased in both groups as compared to the expected normal values. Spinal density did not differ between the two groups, while femoral bone mass was lower in OLTx than in ESLD patients (T-scores of: femoral neck -1.91 +/- 0.16 vs -1.12 +/- 0.22, P < 0.01; total femur -1.62 +/- 0.16 vs -0.94 +/- 0.23, P < 0.02). Bone alkaline phosphatase was the only independent predictor of femoral density (R2 = -0.21, P < 0.05). Symptomatic fractures were reported by 25% of OLTx and 15% of ESLD patients. MXA vertebral fractures were present in 28% of OLTx and 7.5% of ESLD (P < 0.05) patients. Most of these fractures had been asymptomatic. Total methylprednisolone intake was higher in patients with MXA vertebral fractures than in non-fractured patients (P < 0.05). CONCLUSIONS: Fragility fractures, especially of the spine, occur more frequently after liver transplantation, with corticosteroid treatment being the most important risk factor. Morphometric X-ray absorptiometry represents a useful technique for identifying vertebral fractures even in liver transplanted patients.     

Reversal of osteopenia with diet in adult coeliac disease.

To evaluate the effects of a gluten free diet on bone mineral density in untreated adult patients with coeliac disease, 63 patients (17-79 years, 35 women) were examined at diagnosis and after one year taking a gluten free diet. Bone mineral density was measured in the forearm using single photo absorptiometry and in the lumbar spine, femoral neck, and trochanter using dual energy x ray absorptiometry. The values for each patient were compared with those of 25 healthy controls, matched for sex, age, and menopausal state. Before being given a gluten free diet bone mineral density in the total group was reduced at all sites (p < 0.001). Age adjusted bone mineral density was inversely correlated with age. During the first year taking a gluten free diet bone mineral density increased at all sites (p < 0.01). This was seen in patients of all ages and in patients who were without symptoms of malabsorption (weight loss or diarrhoea) before treatment. Low bone mineral density in patients with untreated coeliac disease increases rapidly when treatment with a gluten free diet is followed. These findings emphasise the importance of early diagnosis and treatment in all patients with coeliac disease.     

Effect of a gluten free diet on osteopenia in adults with newly diagnosed coeliac disease.

BACKGROUND/AIMS: Calcium and vitamin D malabsorption in coeliac disease predispose to skeletal demineralisation. This study aimed to determine bone mineral density in patients studied in the first year after diagnosis of coeliac disease, and to detect changes in bone mineral density over the subsequent year. METHODS: Lumbar spine and femoral neck bone mineral density was measured in 21 adults with coeliac disease, diagnosed and started on a gluten free diet during the preceding year, with dual energy x ray absorptiometry and repeated after 12 months. RESULTS: Bone mineral density was significantly lower in patients than in paired controls (matched for age and sex), at lumbar spine (0.819 g/cm2 compared with 1.021 g/cm2, p < 0.001 Wilcoxon signed rank test) and femoral neck (0.663 g/cm2 compared with 0.794 g/cm2, p < 0.001). Repeat measurement after 12 months demonstrated that patients had a significant gain in bone mineral density at lumbar spine (16.6%/year), and femoral neck (15.5%/year, p < 0.002, Wilcoxon signed rank test at both sites), whereas no significant change in bone mineral density was detected in controls. CONCLUSIONS: Treatment of coeliac disease with a gluten free diet is associated with a significant increase in bone mineral density, although patients still had lower bone mineral density than controls.     

Assessment of lactose absorption by measurement of urinary galactose

Individuals with sufficient intestinal lactase hydrolyze ingested lactose to galactose and glucose and these monosaccharides are absorbed. Lactose is not digested completely when intestinal lactase activity is low and the disaccharide is malabsorbed. Breath hydrogen excretion after lactose ingestion is used commonly to diagnose lactose malabsorption. However, no direct tests are currently used to assess lactose absorption. We tested a new method of assessing lactose absorption in 26 healthy individuals. Each subject ingested 50 g of lactose. Participants were evaluated for lactose malabsorption using a standard 3-h breath hydrogen test. In addition, the urinary excretions of galactose, lactose, and creatinine were quantitated for 3-5 h after lactose ingestion. On the basis of breath hydrogen analysis after lactose ingestion, 12 individuals were lactose malabsorbers (defined as a rise in the breath hydrogen concentration of greater than 20 parts per million above the baseline value). The 14 subjects who did not malabsorb lactose by breath hydrogen testing (defined as a rise in the breath hydrogen concentration of less than or equal to 20 parts per million above the baseline value), had significantly more galactose in their urine 1, 2, and 3 h after lactose ingestion than lactose malabsorbers. The ratio of excreted lactose to excreted galactose was significantly decreased in lactose absorbers compared with lactose malabsorbers (p less than 0.001). Determination of the ratio of urinary galactose to urinary creatinine separated lactose absorbers from lactose malabsorbers completely (p less than 0.001). We conclude from this study that the determination of urinary galactose, urinary lactose/galactose ratio, and urinary galactose/creatinine ratio may be used to assess lactose digestion and absorption in healthy adults.     

Antihistamine Therapy and Bone Mineral Density: Analysis in a Population-Based US Sample

Background

Histamine may play an important role in bone turnover. The data regarding histamine 1 receptor antagonist (H1RA), histamine 2 receptor antagonist (H2RA), and bone mineral density in humans are sparse. We examined bone mineral density in subjects using histamine receptor antagonists in a representative US population-based sample from the Third National Health and Nutrition Examination Survey (1988-1994).

Methods

Adult subjects aged 60 years and more using H1RA or H2RA who underwent dual energy x-ray absorptiometry scanning in the Third National Health and Nutrition Examination Survey were identified. We compared the femoral neck bone mineral density among users of these agents with nonusers in adjusted linear regression models that included known demographic, anthropometric, and medical risk factors for osteoporosis.

Results

The mean age of the study subjects was 72.6 years; 52% were women and 59% were white. Among subjects with femoral neck bone mineral density measured, 199 used H1RAs, 297 used H2RAs, and 4162 were nonusers of histamine receptor antagonists. Femoral neck bone mineral density adjusting for age and gender and other covariates was slightly higher in H1RA users (0.74 g/cm²) versus nonusers (0.72 g/cm²; P = .037). H2RA users showed slightly lower adjusted bone mineral density compared with nonusers (0.69 g/cm² vs 0.72 g/cm²; P = .003), but bone densities were similar between H2RA users and nonusers when daily calcium intake exceeded 800 mg per day.

Conclusion

Femoral neck bone mineral density may be higher in H1RA users than nonusers among older adults. H2RA users with reduced calcium intake had lower bone mineral density than nonusers.     

Risk of osteopenia after proctocolectomy and ileal pouch-anal anastomosis for ulcerative colitis

BACKGROUND: The aim of our study was to evaluate the influence of pouchitis and villous atrophy on bone mineral density and metabolism at least 5 years after ileal pouch-anal anastomosis for ulcerative colitis (UC). METHODS: Eighty-eight subjects with a J-pouch operated on between 1985 and 1994, and 20 ulcerative colitis subjects with a conventional ileostomy were enrolled. Endoscopy was performed and spine and femoral neck bone mineral densities measured. Bone metabolism was assessed by measurement of serum levels of parathyroid hormone, osteocalcin, 25-hydroxyvitamin D3, calcium, alkaline phosphatase and urinary N-telopeptide cross-linked of type I collagen (NTX). RESULTS: In the lumbar spine, 37% of the J-pouch subjects with subtotal to total villous atrophy had osteopenia (Z score <-1), whereas none of the subjects with normal villous structure had reduced bone densities in the spine or femoral neck. The highest prevalence of osteopenia (66.7%) and the lowest spine (mean -0.89+/-0.36; P = 0.006) and femoral neck (mean -0.63+/-0.29; P = 0.07) Z scores were found among the patients (n = 12) with inflammation in the proximal limb of the pouch. No biochemical parameters were found to predict osteopenia and in stepwise regression analysis, the only independent risk factors for osteopenia were low body mass index and villous atrophy. CONCLUSIONS: Patients with a J-pouch showing high inflammatory activity and villous atrophy in the pouch need long-term follow-up and should be ensured adequate intake of calcium and vitamin D.     

Development, Validation, and Applicability of a Symptoms Questionnaire for Lactose Malabsorption Screening

Lactase deficiency has a high prevalence worldwide. Thus, a valid symptom scale would be a useful tool for identifying patients with lactose malabsorption. Objective To develop, validate, and apply a symptoms questionnaire on lactose malabsorption to identify lactose malabsorbers diagnosed with the gold-standard hydrogen breath test. Methods In the first part of the study, 292 patients completed a questionnaire at the end of a 50-g lactose breath test. The questionnaire included five items (diarrhea, abdominal cramping, vomiting, audible bowel sounds, and flatulence or gas) scored on a 10-cm visual analogue scale. In the second part of the study, 171 patients completed the questionnaire twice: first, according to their opinion when consuming dairy products at home and second, after a 50-g lactose breath test. Patients were grouped as absorbers or malabsorbers according to the result of the breath test. Results Diarrhea, abdominal cramping, and flatulence were scored significantly higher in malabsorbers than in absorbers. Total score of the symptomatic questionnaire was significantly higher in malabsorbers (17.5 versus 3.0, P < 0.01). According to receiver operator characteristics (ROC) analysis, the most discriminant cut-off of the total score to identify lactose malabsorption was 6.5 (sensitivity 0.75, specificity 0.67). In 58 malabsorbers the effect size of the questionnaire to determine sensitivity to change was 1.32. In the second part of the study, scoring of the home questionnaire was higher than after the lactose-breath test. The lactose malabsorbers rate was higher according to the home questionnaire than after the lactose breath test (72% versus 52%). The home questionnaire had excellent sensitivity (0.82) but low specificity (0.35). Conclusion We developed and validated a five-item symptoms questionnaire for lactose malabsorption. This is a valid test that permits patients with a total score lower than 7 to be excluded from future studies.     

Factors affecting bone mineral density in men

In this study, in 131 men aged 20–75 years, we investigated correlations between bone mineral density (BMD) in the lumbar spine and femoral neck and endogenous factors (age, body mass index) as well as exogenous factors (calcium intake, physical activity, smoking, caffeine, socioeconomic and educational levels). The age had a negative effect on femoral neck BMD in patients overall, and on both lumbar spine and femoral neck BMD in patients under 50. Physical activity has effects on femoral neck BMD in men above 50. Lumbar vertebral BMD negatively correlated with smoking in patients overall, and this correlation persisted when patients aged 50 and older were analyzed separately. Femoral neck BMD was positively correlated with body mass index in men aged 50 and older. Given the variety of findings in the research literature regarding risk factors for low BMD, we suggest that genetic and geographic factors should be considered.     

Lactose malabsorption among the Pima indians of Arizona

Lactose loading tests and other means were used to determine the pattern of primary "adult" lactose malabsorption (LM) and milk use among 171 subjects, including 122 children and 49 adults, almost all of them Pima Indians of Arizona. LM develops at quite young ages in full-blooded Pima children: already in the 3- to 4-year age group, 40% had LM. Of 62 full-blooded Indians (greater than or equal to 4 years of age), 59 (95%) had LM. Of 41 Indians (greater than or equal to 4 years) who were of mixed Indian-northern European ancestry, however, only 25 (61%) had LM, and, among them, prevalence of LM correlated with degree of northern European admixture. Whereas only 21% of Pima lactose absorbers reported symptoms after the loading test, 72% of malabsorbers did so, with older malabsorbers more likely to experience symptoms. In their everyday lives, only 23% of malabsorbers recognized symptoms brought on by milk consumption, but the percentage of malabsorbers making such an association increased with age. Nevertheless the Pima, adults as well as children, continue to drink reasonable quantities of milk. Family pedigrees are consistent with the hypothesis that adult lactose absorption is inherited as an autosomal dominant trait. Over-all results of this study, moreover, support the geographic hypothesis advanced to explain ethnic or racial differences in prevalence of LM, rather than the induction hypothesis.     

Increased bone volume and bone mineral content in xylitol-fed aged rats.

BACKGROUND: Our previous studies have shown that dietary xylitol supplementation protects against the loss of bone mineral after ovariectomy. The ovariectomy-induced decrease in trabecular bone volume is significantly retarded by dietary xylitol. Objective: To study whether dietary xylitol can protect against bone loss also during aging, a long-term experimental study was performed with rats. METHODS: Twenty-four male Sprague-Dawley rats were divided into two groups. The rats in the control group were fed a basal RM1 diet, while the rats in the experimental group were continuously fed the same diet supplemented with 10% (w/w) xylitol. The rats were killed after 20 months. Their tibiae were used for the analyses of bone density and trabecular bone volume, and their femurs were used for the scanning analyses with peripheral quantitative computed tomography (pQCT). RESULTS: The tibial density of the xylitol-fed aged group (1.73 +/- 0.14 g/mm(3)) was significantly greater than that of the aged group without xylitol (1.56 +/- 0.14 g/ mm(3)). The trabecular bone volume of the xylitol-fed rats was 21.2 +/- 4.0%. It was significantly greater than that of the rats not receiving xylitol (9.3 +/- 4.3%). The pQCT-measured cortical bone mineral density and the pQTC-measured cortical bone mineral content of the femoral diaphysis were significantly greater in the xylitol-fed group than in the control group. The trabecular bone mineral density and the trabecular bone mineral content of the femoral distal metaphysis were also significantly greater in the xylitol-fed group than in the non-xylitol group. The total bone mineral density and the total bone mineral content of the femoral neck in the xylitol-fed aged group significantly exceeded those in the aged group without xylitol supplementation. CONCLUSIONS: A continuous moderate dietary xylitol supplementation leads to increased bone volume and increased bone mineral content in the long bones of aged rats. This indicates a xylitol-induced protection against aging-related osteoporotic changes.     

TNF-alpha gene polymorphism and plasma TNF-alpha levels are related to lumbar spine bone area in healthy female Caucasian adolescents

OBJECTIVE: The cytokine tumor necrosis factor alpha (TNF-alpha) is an important regulator of bone metabolism. Polymorphisms in the promoter region of the TNF-alpha gene at positions -308 and -863 have been identified. We investigated whether these polymorphisms and circulating TNF-alpha levels were related to bone mineral density and bone area in adolescent girls. DESIGN: Bone mineral density (BMD), bone area (BA), anthropometric characteristics and biochemical analyses were measured in adolescent girls and compared with regard to TNF-alpha genotype. METHODS: Allelic variants of the TNF-alpha gene in 97 girls, aged 16.9+/-1.2 years (mean+/-S.D.), were identified using polymerase chain reaction and the restriction endonucleases NcoI and TaiI. Bone mineral density and bone area of the femoral neck, lumbar spine and total body were measured using dual energy X-ray absorptiometry. RESULTS: Carriers of the rare -863 A allele (n=25) had higher body weight (P=0.03), lumbar spine BMD (P=0.02), and larger total BA (P=0.03), femoral neck area (P<0.05), and lumbar spine area (P=0.01). The independent predictors of BMD and BA were investigated using multiple regression. The TNF-alpha-863 genotypes (beta=0.18, P=0.03) and the TNF-alpha plasma levels (beta=0.19, P=0.04) independently predicted BA of the lumbar spine but not BA or BMD of any other measured sites. No statistically significant differences in body constitution parameters, biochemical parameters, bone density, or bone area at the measured skeletal sites were found when comparing the groups defined by the allelic variants at position -308 (P=0.17-0.84). CONCLUSIONS: We found the TNF-alpha-863 polymorphism and the TNF-alpha plasma levels to be independent predictors of lumbar spine area in healthy Caucasian adolescent females.     

Profiles of endogenous circulating cortisol and bone mineral density in healthy elderly men.

Exogenous glucocorticoids are known to increase the risk of osteoporosis. However, the contribution made by endogenous circulating cortisol concentrations to adult skeletal status remains unknown. We examined this issue in a sample of 34 healthy men, aged 61-72 yr. Venous blood samples were obtained under standard conditions every 20 min over a 24-h period. Measurements were made of serum cortisol and cortisol-binding globulin. Bone mineral density was measured at the lumbar spine and proximal femur using dual energy x-ray absorptiometry. Measurements were made at baseline and 4 yr later. There was a weak negative association between integrated cortisol concentration and lumbar spine bone density (r = -0.37; P < 0.05); similar relationships (P < 0.05) existed at three of five proximal femoral sites. There were also statistically significant positive associations between the trough cortisol concentration and bone loss rate at the lumbar spine (r = 0.38; P < 0.05), femoral neck (r = 0.47; P < 0.001), and the trochanteric region (r = 0.41; P = 0.02) over the 4-yr follow-up period. The cross-sectional relationships between cortisol concentration and bone density were removed by adjustment for body mass index, but the influence on bone loss rate remained significant after adjusting for adiposity, cigarette smoking, alcohol consumption, dietary calcium intake, physical activity, and serum testosterone and estradiol levels. These observations suggest that the endogenous cortisol profile of healthy elderly men is a determinant of their bone mineral density and their rate of involutional bone loss.