See related commentary by Kanis, page [1829][1]

Since the publication of the Osteoporosis Canada guidelines in 2002, there has been a paradigm shift in the prevention and treatment of osteoporosis and fractures. [1][2],[2][3] The focus now is on preventing fragility fractures and their negative

/pdf/2010-clinical-practice-guidelines-for-the-diagnosis-and-4ttqfkm9wl.pdf

2010 clinical practice guidelines for the diagnosis and management of osteoporosis in Canada: summary

Background: Treatment intervention thresholds for prevention of osteoporotic fractures can be derived from reports from the World Health Organization (diagnostic criteria) and National Osteoporosis Foundation (treatment criteria). It is not known how well these thresholds work to identify women who will fracture and are therefore candidates for treatment interventions. We used data from the National Osteoporosis Risk Assessment (NORA) to examine the effect of different treatment thresholds on fracture incidence and numbers of women with fractures within the year following bone mineral density measurement. Methods: The study comprised 149 524 white postmenopausal women aged 50 to 104 years (mean age, 64.5 years). At baseline, bone mineral density was assessed by peripheral bone densitometry at the heel, finger, or forearm. New fractures during the next 12 months were self-reported. Results: New fractures were reported by 2259 women, including 393 hip fractures; only 6.4% had baseline T scores of �2.5 or less (World Health Organization definition for osteoporosis). Although fracture rates were highest in these women, they experienced only 18% of the osteoporotic fractures and 26% of the hip fractures. By National Osteoporosis Foundation treatment guidelines, 22.6% of the women had T scores of 2.0 or less, or �1.5 or less with 1 or more clinical risk factors. Fracture rates were lower, but 45% of osteoporotic fractures and 53% of hip fractures occurred in these women. Conclusions: Using peripheral measurement devices, 82% of postmenopausal women with fractures had T scores better than �2.5. A strategy to reduce overall fracture incidence will likely require lifestyle changes and a targeted effort to identify and develop treatment protocols for women with less severe low bone mass who are nonetheless at increased risk for future fractures.

/pdf/bone-mineral-density-thresholds-for-pharmacological-ei0nj7qdsn.pdf

Bone mineral density thresholds for pharmacological intervention to prevent fractures

The Scottish Mental Surveys of 1932 and 1947 collected valid IQ-type test scores for almost everyone born in 1921 and 1936 and attending school on June 1, 1932 (N=89,498) and June 4, 1947 (N=70,805). These surveys are described. This research, using the surveys' data, examined (a) the stability of intelligence differences across the life span, (b) the determinants of cognitive change from childhood to old age, and (c) the impact of childhood intelligence on survival and health in old age. Surviving participants of the Scottish Mental Surveys were tested, and the surveys' data were linked with public and health records. Novel findings on the stability of IQ scores from age 11 to age 80; sex differences in cognitive aging; the dedifferentiation hypothesis of cognitive aging; and the effect of childhood IQ on all-cause and specific mortality, morbidity, and frailty in old age are presented.

/pdf/the-impact-of-childhood-intelligence-on-later-life-following-5ckui6xpr1.pdf

The impact of childhood intelligence on later life: following up the Scottish mental surveys of 1932 and 1947.

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(02)08827-X.pdf

Treatment of postmenopausal osteoporosis.

We attempted to investigate whether vitamin K2 (menatetrenone) treatment effectively prevents the incidence of new fractures in osteoporosis. A total of 241 osteoporotic patients were enrolled in a 24-month randomized open label study. The control group (without treatment; n = 121) and the vitamin K2-treated group (n = 120), which received 45 mg/day orally vitamin K2, were followed for lumbar bone mineral density (LBMD; measured by dual-energy X-ray absorptiometry [DXA]) and occurrence of new clinical fractures. Serum level of Glu-osteocalcin (Glu-OC) and menaquinone-4 levels were measured at the end of the follow-up period. Serum level of OC and urinary excretion of deoxypyridinoline (DPD) were measured before and after the treatment. The background data of these two groups were identical. The incidence of clinical fractures during the 2 years of treatment in the control was higher than the vitamin K2-treated group (chi2 = 10.935; p = 0.0273). The percentages of change from the initial value of LBMD at 6, 12, and 24 months after the initiation of the study were -1.8 +/- 0.6%, -2.4 +/- 0.7%, and -3.3 +/- 0.8% for the control group, and 1.4 +/- 0.7%, -0.1 +/- 0.6%, and -0.5 +/- 1.0% for the vitamin K2-treated group, respectively. The changes in LBMD at each time point were significantly different between the control and the treated group (p = 0.0010 for 6 months, p = 0.0153 for 12 months, and p = 0.0339 for 24 months). The serum levels of Glu-OC at the end of the observation period in the control and the treated group were 3.0 +/- 0.3 ng/ml and 1.6 +/- 0.1 ng/ml, respectively (p < 0.0001), while the serum level of OC measured by the conventional radioimmunoassay (RIA) showed a significant rise (42.4 +/-6.9% from the basal value) in the treated group at 24 months (18.2 +/- 6.1% for the controls;p = 0.0081). There was no significant change in urinary DPD excretion in the treated group. These findings suggest that vitamin K2 treatment effectively prevents the occurrence of new fractures, although the vitamin K2-treated group failed to increase in LBMD. Furthermore, vitamin K2 treatment enhances gamma-carboxylation of the OC molecule.

Vitamin K2 (Menatetrenone) Effectively Prevents Fractures and Sustains Lumbar Bone Mineral Density in Osteoporosis

The phenotypes of apolipoprotein E (Apo E) and their relationship with the bone mineral density (BMD) were examined in 284 unrelated postmenopausal Japanese women aged 47-82 years (64.0 ± 1.0 years, mean ± SE). The Apo E phenotype was analyzed by the isoelectric focusing method, followed by immunoblotting. The relationship between the Apo E phenotype and the vitamin D receptor (VDR) gene or estrogen receptor (ER) gene genotypes was also studied in the same population. The Apo E phenotypic frequencies in our population were 9.9% for E3/2, 66.5% for E3/3, 1.8% for E4/2, 19.7% for E4/3, and 2.1% for E4/4. We classified these phenotypes into three categories: Apo E4-/- (E3/2 and E3/3, n = 217), Apo E4+/- (E4/3 and E4/2, n = 61), and Apo E4+/+ (E4/4, n = 6). The age, body weight, body height, and years since menopause were not significantly different among these three categories. The lumbar BMD values in these three groups were significantly different in the order of E4-/- (0.91 ± 0.01 g/cm 2 ), E4+/- (0.85 ± 0.02 g/cm 2 ), and E4+/+ (0.83 ± 0.06 g/cm 2 ) (p = 0.031). The same trend was also observed for the Z score of the total BMD (p = 0.022). The serum level of intact osteocalcin in E4+/+ (15.2 ± 5.7 ng/ml) was higher than in E4-/- (7.7 ± 0.3 ng/ml) or E4+/- (7.7 ± 0.7 ng/ml) (p = 0.004 by analysis of variance). However, there were no other significant differences in the serum or urinary levels of bone turnover markers. Serum cholesterol in the E4+/+ group tended to be higher than in the other two groups (p = 0.05). There were no significant associations of the VDR and ER genotypes with the Apo E4 phenotype. A multivariate linear regression analysis revealed Apo E4 to be a significant, independent predictor of the Z score of the lumbar BMD. The effect of the Apo E4 allele on the Z score of the lumbar BMD (-0.493 ± 0.152) was not significantly different from that in the AAB of VDR (-0.616 ± 0.225) or PPxx of ER (-0.785 ± 0314). In conclusion, the Apo E4 allele is associated with a low bone mass in postmenopausal Japanese.

Association of bone mineral density with apolipoprotein E phenotype.

Assessment of bone density in the distal radius with computer assisted X-ray densitometry (CXD).

In order to compare the bone aging process in Werner's syndrome, a disease characterized by premature aging, and that in natural aging, we have assessed the bone status in a total of 19 cases (11 males and eight postmenopausal females) with Werner's syndrome. The spinal deformity index was determined for a total of 87 vertebral bodies from nine male patients and for a total of 61 vertebral bodies from six female patients. In the male patients, 15 vertebral deformities among 87 vertebrae in seven patients were observed, and the incidences of patients bearing deformity and deformed vertebrae were 77.8 (7/9) and 17.2% (15/87), respectively. In the female patients, the corresponding incidences were 50.0% (3/6) and 4.9% (3/61), respectively. The chi2-values for the incidences of patients bearing deformity and deformed vertebrae in the male and the female patients were 1.25 (P=0.26) and 5.24 (P<0.03), respectively. The metacarpal cortical thickness (MCI) was also measured on hand X-ray films, and the Z scores for MCI in the male (n=9) and female (n=3) patients were -0.8+/-0.3 and -1.6+/-0.3, respectively. This gender-based difference in the MCI was not statistically significant but, the Z scores for MCI in both the males and the females were significantly smaller than those of corresponding age-matched controls (P<0.05 and 0.01, respectively). The serum levels of calcium, intact PTH, 25-OH vitamin D and 1,25(OH)2 vitamin D in three male and three female Werner's syndrome patients were within the reference ranges with one exception. The serum intact osteocalcin levels in the male (2.2+/-0.6 ng/ml) and female (2.6+/-0.8 ng/ml) patients were lower than the age-matched control values (P<0.05 for males) and the postmenopausal control values (P<0.05 for females). In conclusion, the incidence of spinal bone deformity was higher in males with Werner's syndrome than that in female patients. The cortical bone thickness decreased in both the male and the female patients. A low serum intact osteocalcin level was a characteristic finding in the male and in post-menopausal Werner's syndrome, so that the bone changes such as vertebral fracture incidence and the serum intact osteocalcin level in Werner's syndrome may differ from those in normal aging in the general population.

Bone and Calcium Metabolism in Werner's Syndrome

Purpose: To evaluate the effect of disuse on bone mineral content (BMC), lean mass, and fat mass.Method and subjects: We obtained BMC, lean mass, and fat mass from measurements of each side of the arm and the leg in 20 women with unilateral hip osteoarthritis and 63 normal women using a whole-body dual-energy X-ray absorptiometry (DXA) scan. The ratio of the affected side to the unaffected side (A-U ratio) was calculated for BMC, lean mass, and fat mass in the arm and the leg.Results: A significant intergroup difference in the A-U ratio was noted for leg BMC (0.85vs 0.99,P<0.01), and for lean mass of the leg (0.88vs 0.99,P<0.01). When leg BMC was adjusted with lean mass, this intergroup difference became insignificant.Conclusion: This study reconfirmed that a decrease in BMC and lean mass can result from disuse. We suggest that a large portion of BMC loss in the immobilized leg might be a secondary change resulting from lean mass loss.

Effect of disuse on bone mineral content, lean mass, and fat mass in osteoarthritic patients

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