Bone Area Mineral Content Research Articles

Effect of Leptin Deficiency on the Skeletal Response to Hindlimb Unloading in Adult Male Mice

Based on body weight, morbidly obese leptin-deficient ob/ob mice have less bone than expected, suggesting that leptin plays a role in the skeletal response to weight bearing. To evaluate this possibility, we compared the skeletal response of wild type (WT) and ob/ob mice to hindlimb unloading (HU). Mice were individually housed at 32 °C (thermoneutral) from 4 weeks of age (rapidly growing) to 16 weeks of age (approaching skeletal maturity). Mice were then randomized into one of 4 groups (n = 10/group): (1) WT control, (2) WT HU, (3) ob/ob control, and (4) ob/ob HU and the results analyzed by 2-way ANOVA. ob/ob mice pair-fed to WT mice had normal cancellous bone volume fraction (BV/TV) in distal femur, lower femur length and total bone area, mineral content (BMC) and density (BMD), and higher cancellous bone volume fraction in lumbar vertebra (LV). HU resulted in lower BMC and BMD in total femur, and lower BV/TV in distal femur and LV in both genotypes. Cancellous bone loss in femur in both genotypes was associated with increases in osteoclast-lined bone perimeter. In summary, leptin deficiency did not attenuate HU-induced osteopenia in male mice, suggesting that leptin is not required for bone loss induced by unweighting.

Long‐chain Polyunsaturated Fatty Acid Status Associates with Bone Mass in Overweight and Obese Children

Children who are obese are at increased risk of fractures. However, linkages to possible nutritional imbalances are unclear. Experimental studies suggest long‐chain polyunsaturated fatty acids (LCPUFA) such as arachidonic acid (AA C20:4 n6) modulate bone mass in a biphasic manner, yet it is uncertain whether this is observed in humans. This study examined the relationship between LCPUFA status and bone mass in overweight and obese (OvOb) children. Participants (n=119, 9.28 ± 1.89 y, BMI‐z 3.03 ± 1.02) were assessed for bone mass with DXA (Hologic Discovery). Fatty acid profile was measured in red blood cells (RBC) using gas chromatography. A generalized linear model was used to determine relationships between LCPUFA in RBC and bone outcomes with adjustments for Tanner stages and BMI. Saturated fatty acids palmitate (C16:0) and stearate (C18:0) inversely related to lumbar spine bone mineral density (r=‐0.18 and ‐0.22 respectively, p<0.05); while the omega‐3 fatty acid α‐linoleneate (ALA, C18:3 n3) positively related to whole body, total hip, ultra‐distal and mid forearm bone area, mineral content (BMC) and density (r=0.21 to 0.31, p<0.05). When children were divided into three groups by AA tertiles (cutoffs by 33rd and 67th percentile of % total FA) and compared with MIXED model ANOVA, those in the second tertile had greater forearm bone area and BMC than those in the first or third tertiles (Table 1), indicating higher AA levels may not confer additional benefits in bone growth and mineral accrual. These data suggest LCPUFA may play important roles in modulating bone mass during growth in OvOb children. 1st tertile (n=39) [4.67‐7.51%] 2nd tertile (n=35)[7.52‐ 8.42%] 3rd tertile (n=45)[8.44‐14.06%] Ultra‐dista Area (cm2) 4.09 ± 0.64a 4.67 ± 0.67b 4.29 ± 0.63a BMC (g) 1.32 ± 0.05 1.51 ± 0.09 1.38 ± 0.07 Mid Area (cm2) 7.50 ± 0.47ab 9.21 ± 0.55a 7.75 ± 0.32b BMC (g) 3.05 ± 0.22a 4.02 ± 0.34b 3.31 ± 0.19a 1/3 distal Area (cm2) 4.33 ± 0.10a 4.74 ± 0.10b 4.38 ± 0.06a BMC (g) 2.11 ± 0.09 2.43 ± 0.13 2.28 ± 0.09

Regional changes in bone area and bone mineral content in boys with Duchenne muscular dystrophy (DMD) receiving steroid therapy

OBJECTIVE To examine the functional and skeletal effects of 30 months of steroid treatment in boys with Duchenne muscular dystrophy. STUDY DESIGN Lumbar spine (L(2)L(4)) and subcranial dual energy X-ray absorptiometry scanning was performed on 25 boys (mean age 7.4 years) at baseline and after 30 months of steroid treatment. RESULTS At baseline, L(2)L(4) bone mineral content (BMC) was significantly low for projected bone area although appropriate for reduced lean body mass (LBM). Subcranial bone area for height and subcranial BMC for area and LBM were all significantly reduced. After 30 months of steroid therapy there was a significant increase in subcranial bone area for height but a significant reduction of subcranial BMC for area. At the lumbar spine there were no significant changes in bone area but small increases in L(2)L(4) BMC both for bone area and LBM. CONCLUSION At baseline reduced mechanical load from diminished muscle function results in narrow light bones more noticeable in the subcranial region than the lumbar spine. Increases observed in subcranial bone area at 30 months suggest a gradual adaptation to increased gravitational load whereas at the spine there were no apparent detrimental effects on bone after 30 months of steroid therapy.

(n-3) Fatty Acids Reduce the Release of Prostaglandin E2 from Bone but Do Not Affect Bone Mass in Obese (fa/fa) and Lean Zucker Rats ,

Childhood obesity is prevalent and linked to the development of Type 2 diabetes mellitus (DM) and poor bone health. Some PUFA enhance bone mass and thus may improve bone health in obese children. The study objective was to determine the effects of dietary (n-6) compared with (n-3) essential PUFA and long-chain PUFA (LCPUFA) on bone in an obese and insulin-resistant state. Male fa/fa (n = 48) and lean Zucker rats (n = 48) were fed diets containing safflower oil [SO, high (n-6) PUFA], flaxseed oil [FXO, high (n-3) PUFA], or menhaden oil [MO, high (n-3) LCPUFA] for 9 wk. Measurements included the following: femur bone area (BA), mineral content (BMC), density (BMD), morphometry and ex vivo release of prostaglandin E(2) (PGE(2)); plasma osteocalcin and C-terminal telopeptides of type I collagen. Differences among groups were detected using 2-way ANOVA. Genotype effects in the fa/fa rats included lower femoral weight, length, BA, and BMC, as well as femoral head and proximal epiphysis widths compared with the lean rats, but BMD was not affected. Femur BA, BMC, and BMD did not differ among the dietary groups, but diaphysis width was elevated in the MO group and PGE(2) release was reduced by the FXO and MO diets. No genotype x diet interactions were observed. These data indicate that the fa/fa Zucker rat is at risk for low bone mass and that dietary (n-3) FA effectively reduce PGE(2) release. Whether reduced PGE(2) will support optimal peak bone mass during childhood and conserve bone mass with aging warrants investigation.

Low Levels of Dietary Arachidonic and Docosahexaenoic Acids Improve Bone Mass in Neonatal Piglets, but Higher Levels Provide No Benefit ,

In piglets, feeding arachidonic acid (AA) and docosahexaenoic acid (DHA) in a 5:1 ratio leads to elevated bone mass, but the optimal total quantity requires clarification. We studied bone mass and modeling of piglets that were randomized to receive 1 of 4 formulas for 15 d: control formula or the same formula with various levels of AA:DHA (0.5:0.1 g, 1.0:0.2 g or 2.0:0.4 g AA:DHA/100 g of fat). Measurements included: bone area (BA), mineral content (BMC), and density (BMD) of whole body, lumbar spine, and excised femurs; biomarkers of bone modeling were plasma osteocalcin and urinary cross-linked N-telopeptides of type 1 collagen (NTx), tibial ex vivo release of prostaglandin E(2) (PGE(2)), plasma insulin-like growth factor-1 (IGF-1), and tissue fatty acids. Main effects were identified using ANOVA and post hoc Bonferroni t tests. In supplemented piglets, relations among liver fatty acid proportions and bone mass were assessed using Pearson correlations. Whole body (P = 0.028) and lumbar spine (P = 0.043) BMD were higher in the group supplemented with 0.5:0.1 g AA:DHA/100 g of fat than in controls. Tissue AA and DHA increased in proportion to diet levels. Liver eicosapentaenoic acid (EPA) correlated positively (r > or = 0.38, P < or = 0.05) with whole body and femur BMC and BMD and lumbar spine BMC. Liver AA:EPA ratio correlated negatively (r > or = -0.039, P < or = 0.05) with whole body, femur, and lumbar spine BMC plus whole body and femur BMD. Dietary 1.0:0.2 g AA:DHA/100 g reduced NTx relative to 2.0:0.4 g AA:DHA/100 g of fat (P = 0.039). The diets did not affect the other biochemical variables measured. Low levels of dietary AA:DHA (0.5:0.1 g/100 g of fat) elevate bone mass, but higher amounts are not beneficial.