PTH and 1.25 vitamin D response to a low-calcium diet is associated with bone mineral density in renal stone formers

BACKGROUND: Renal calcium stones and hypercalciuria are associated with a reduced bone mineral density (BMD). Therefore, the effect of changes in calcium homeostasis is of interest for both stones and bones. We hypothesized that the response of calciuria, parathyroid hormone (PTH) and 1.25 vitamin D to changes in dietary calcium might be related to BMD. METHODS: A single-centre prospective interventional study of 94 hyper- and non-hypercalciuric calcium stone formers consecutively retrieved from our stone clinic. The patients were investigated on a free-choice diet, a low-calcium diet, while fasting and after an oral calcium load. Patient groups were defined according to lumbar BMD (z-score) obtained by dual X-ray absorptiometry (group 1: z-score <-0.5, n = 30; group 2: z-score -0.5-0.5, n = 36; group 3: z-score >0.5, n = 28). The effect of the dietary interventions on calciuria, 1.25 vitamin D and PTH in relation to BMD was measured. RESULTS: An inverse relationship between BMD and calciuria was observed on all four calcium intakes (P = 0.009). On a free-choice diet, 1.25 vitamin D and PTH levels were identical in the three patient groups. However, the relative responses of 1.25 vitamin D and PTH to the low-calcium diet were opposite in the three groups with the highest increase of 1.25 vitamin D in group 1 and the lowest in group 3, whereas PTH increase was most pronounced in group 3 and least in group 1. CONCLUSION: Calcium stone formers with a low lumbar BMD exhibit a blunted response of PTH release and an apparently overshooting production of 1.25 vitamin D following a low-calcium diet.

The systemic angiogenic response during bone healing

INTRODUCTION: Angiogenesis is known to be a critical and closely regulated step during bone formation and fracture healing driven by a complex interaction of various cytokines. Delays in bone healing or even nonunion might therefore be associated with altered concentrations of specific angiogenic factors. These alterations might in turn be reflected by changes in serum concentrations. METHOD: To determine physiological time courses of angiogenic cytokines during fracture healing as well as possible changes associated with failed consolidation, we prospectively collected serum samples from patients who had sustained surgical treatment for a long bone fracture. Fifteen patients without fracture healing 4 months after surgery (nonunion group) were matched to a collective of 15 patients with successful healing (union group). Serum concentrations of angiogenin (ANG), angiopoietin 2 (Ang-2), basic fibroblast growth factor (bFGF), platelet derived growth factor AB (PDGF-AB), pleiotrophin (PTN) and vascular endothelial growth factor (VEGF) were measured using enzyme linked immunosorbent assays over a period of 24 weeks. RESULTS: Compared to reference values of healthy uninjured controls serum concentrations of VEGF, bFGF and PDGF were increased in both groups. Peak concentrations of these cytokines were reached during early fracture healing. Serum concentrations of bFGF and PDGF-AB were significantly higher in the union group at 2 and 4 weeks after the injury when compared to the nonunion group. Serum concentrations of ANG and Ang-2 declined steadily from the first measurement in normal healing fractures, while no significant changes over time could be detected for serum concentrations of these factures in nonunion patients. PTN serum levels increased asymptotically over the entire investigation in timely fracture healing while no such increase could be detected during delayed healing. CONCLUSION: We conclude that fracture healing in human subjects is accompanied by distinct changes in systemic levels of specific angiogenic factors. Significant alterations of these physiologic changes in patients developing a fracture nonunion over time could be detected as early as 2 (bFGF) and 4 weeks (PDGF-AB) after initial trauma surgery.

Effect of two bioabsorbable barrier membranes on bone regeneration of standardized defects in calvarial bone: a comparative histomorphometric study in pigs

BACKGROUND: The effect of two different bioabsorbable collagen membranes on bone regeneration was assessed in standardized, membrane-protected calvarial defects in pigs. METHODS: Two standardized defect types (6 x 6 x 6 mm and 9 x 9 x 9 mm) were produced in the calvaria of pigs: empty defects without a membrane (group 1; eight defects per size); defects filled with deproteinized bovine bone mineral (DBBM) without a membrane (group 2; eight defects per size); defects filled with DBBM and covered by a collagen membrane (group 3; eight defects per size); and defects filled with DBBM and covered by a cross-linked collagen membrane (CCM) (group 4; eight defects per size). Sacrifice took place 16 weeks after surgery, and the following parameters were analyzed: descriptive histology; semiquantitative histology (SQH), assessing bone regeneration in the whole defect area; and histomorphometric analysis of the percentage of bone and DBBM in the regenerated area at three different depth levels of the defect. RESULTS: Using SQH, both membrane types resulted in significantly better bone regeneration compared to groups 1 and 2, irrespective of the defect size (P <0.005), with no difference between the two membranes. In the histomorphometric analysis, the layer immediately below the surface exhibited a significantly higher percentage of bone in groups 3 (27%) and 4 (36%) versus the two other groups for the 9 x 9 x 9-mm defects. No such differences were apparent for the 6 x 6 x 6-mm defects or the other two depth levels (bottom and middle layer) for either defect size. CONCLUSIONS: The two collagen membranes tested significantly enhanced bone regeneration, especially in the superficial level of the calvarial bone defects. The prototype CCM did not provide any further advantage in the present animal model.

Cortical and trabecular bone mineral density in transsexuals after long-term cross-sex hormonal treatment: a cross-sectional study

The aim of this study was to explore the effect of long-term cross-sex hormonal treatment on cortical and trabecular bone mineral density and main biochemical parameters of bone metabolism in transsexuals. Twenty-four male-to-female (M-F) transsexuals and 15 female-to-male (F-M) transsexuals treated with either an antiandrogen in combination with an estrogen or parenteral testosterone were included in this cross-sectional study. BMD was measured by DXA at distal tibial diaphysis (TDIA) and epiphysis (TEPI), lumbar spine (LS), total hip (HIP) and subregions, and whole body (WB) and Z-scores determined for both the genetic and the phenotypic gender. Biochemical parameters of bone turnover, insulin-like growth factor-1 (IGF-1) and sex hormone levels were measured in all patients. M-F transsexuals were significantly older, taller and heavier than F-M transsexuals. They were treated by cross-sex hormones during a median of 12.5 years before inclusion. As compared with female age-matched controls, they showed a significantly higher median Z-score at TDIA and WB (1.7+/-1.0 and 1.8+/-1.1, P < 0.01) only. Based on the WHO definition, five (who did not comply with cross-sex hormone therapy) had osteoporosis. F-M transsexuals were treated by cross-sex hormones during a median of 7.6 years. They had significantly higher median Z-scores at TEPI, TDIA and WB compared with female age-matched controls (+0.9+/-0.2 SD, +1.0+/-0.4 SD and +1.4+/-0.3 SD, respectively, P < 0.0001 for all) and reached normal male levels except at TEPI. They had significantly higher testosterone and IGF-1 levels (p < 0.001) than M-F transsexuals. We conclude that in M-F transsexuals, BMD is preserved over a median of 12.5 years under antiandrogen and estrogen combination therapy, while in F-M transsexuals BMD is preserved or, at sites rich in cortical bone, is increased to normal male levels under a median of 7.6 years of androgen treatment in this cross sectional study. IGF-1 could play a role in the mediation of the effect of androgens on bone in F-M transsexuals.

Effects of deflazacort versus prednisone on bone mass, body composition, and lipid profile: a randomized, double blind study in kidney transplant patients

To compare the effects of deflazacort (DEFLA) vs. prednisone (PRED) on bone mineral density (BMD), body composition, and lipids, 24 patients with end-stage renal disease were randomized in a double blind design and followed 78 weeks after kidney transplantation. BMD and body composition were assessed using dual energy x-ray absorptiometry. Seventeen patients completed the study. Glucocorticosteroid doses, cyclosporine levels, rejection episodes, and drop-out rates were similar in both groups. Lumbar BMD decreased more in PRED than in DEFLA (P < 0.05), the difference being particularly marked after 24 weeks (9.1 +/- 1.8% vs. 3.0 +/- 2.4%, respectively). Hip BMD decreased from baseline in both groups (P < 0.01), without intergroup differences. Whole body BMD decreased from baseline in PRED (P < 0.001), but not in DEFLA. Lean body mass decreased by approximately 2.5 kg in both groups after 6-12 weeks (P < 0.001), then remained stable. Fat mass increased more (P < 0.01) in PRED than in DEFLA (7.1 +/- 1.8 vs. 3.5 +/- 1.4 kg). Larger increases in total cholesterol (P < 0.03), low density lipoprotein cholesterol (P < 0.01), lipoprotein B2 (P < 0.03), and triglycerides (P = 0.054) were observed in PRED than in DEFLA. In conclusion, using DEFLA instead of PRED in kidney transplant patients is associated with decreased loss of total skeleton and lumbar spine BMD, but does not alter bone loss at the upper femur. DEFLA also helps to prevent fat accumulation and worsening of the lipid profile.

Aromatase deficiency in a female who is compound heterozygote for two new point mutations in the P450arom gene: impact of estrogens on hypergonadotropic hypogonadism, multicystic ovaries, and bone densitometry in childhood

We report on a female who is compound heterozygote for two new point mutations in the CYP19 gene. The allele inherited from her mother presented a base pair deletion (C) occurring at P408 (CCC, exon 9), causing a frameshift that results in a nonsense codon 111 bp (37 aa) further down in the CYP19 gene. The allele inherited from her father showed a point mutation from G-->A at the splicing point (canonical GT to mutational AT) between exon and intron 3. This mutation ignores the splice site and a stop codon 3 bp downstream occurs. Aromatase deficiency was already suspected because of the marked virilization occurring prepartum in the mother, and the diagnosis was confirmed shortly after birth. Extremely low levels of serum estrogens were found in contrast to high levels of androgens. Ultrasonographic follow-up studies revealed persistently enlarged ovaries (19.5-22 mL) during early childhood (2 to 4 yr) which contained numerous large cysts up to 4.8 x 3.7 cm and normal-appearing large tertiary follicles already at the age of 2 yr. In addition, both basal and GnRH-induced FSH levels remained consistently strikingly elevated. Low-dose estradiol (E2) (0.4 mg/day) given for 50 days at the age of 3 6/12 yr resulted in normalization of serum gonadotropin levels, regression of ovarian size, and increase of whole body and lumbar spine (L1-L4) bone mineral density. The FSH concentration and ovarian size returned to pretreatment levels shortly (150 days) after cessation of E2 therapy. Therefore, we recommend that affected females be treated with low-dose E2 in amounts sufficient to result in physiological prepubertal E2 concentrations using an ultrasensitive estrogen assay. However, E2 replacement needs to be adjusted throughout childhood and puberty to ensure normal skeletal maturation and adequate adolescent growth spurt, normal accretion of bone mineral density, and, at the appropriate age, female secondary sex maturation.

Different effects of cyclosporin A on bone remodeling in young and adult rats

Reported effects of cyclosporin A (Sandimmun, CsA) on bone have been both contradictory and controversial. Thus, stimulation of new bone formation as well as increased mineral and matrix resorption have been observed. To investigate the response of basal mineral and matrix turnover to CsA treatment at different stages of skeletal development, comparative experiments were conducted in young growing female rats and in adults. Fifty-six young animals (study A) and 40 adults (study B) received orally either the carrier substance or 5, 15, and 30 mg/kg CsA for 30 days. The following parameters were measured: (a) total skeletal mineral content by dual energy X-ray absorptiometry (DEXA) on days 1 and 30; (b) tibial trabecular volume at day 30; (c) serum osteocalcin at 5-day intervals; (d) urinary deoxypyridinoline (Dpd) excretion (days 1, 15, and 30); and (e) plasma levels of CsA. Results can be summarized as follows: in young rats (study A), total skeletal mineral was not modified by the 5- and 15-mg/kg doses of CsA, whereas 30 mg/kg induced a significant decrease (-15%, p < 0.01). This parameter was not significantly modified in adult animals (study B) subjected to the same doses. The administration of 5 mg/kg CsA did not alter tibial trabecular volume in young rats, but 15 and 30 mg/kg significantly lowered this parameter (-16.3%, p < 0.02, and -42%, p < 0.001, respectively). In adult rats, tibial trabecular volume remained unchanged with the exception of the group receiving 30 mg/kg which exhibited significantly lower values (-28%, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

In vitro evaluation of demineralized freeze-dried bone allograft in combination with enamel matrix derivative

BACKGROUND Preclinical and clinical studies suggest that a combination of enamel matrix derivative (EMD) with demineralized freeze-dried bone allograft (DFDBA) may improve periodontal wound healing and regeneration. To date, no single study has characterized the effects of this combination on in vitro cell behavior. The aim of this study is to test the ability of EMD to adsorb to the surface of DFDBA particles and determine the effect of EMD coating on downstream cellular pathways such as adhesion, proliferation, and differentiation of primary human osteoblasts and periodontal ligament (PDL) cells. METHODS DFDBA particles were precoated with EMD or human blood and analyzed for protein adsorption patterns via scanning electron microscopy. Cell attachment and proliferation were quantified using a commercial assay. Cell differentiation was analyzed using real-time polymerase chain reaction for genes encoding Runx2, alkaline phosphatase, osteocalcin, and collagen 1α1, and mineralization was assessed using alizarinred staining. RESULTS Analysis of cell attachment revealed no significant differences among control, blood-coated, and EMD-coated DFDBA particles. EMD significantly increased cell proliferation at 3 and 5 days after seeding for both osteoblasts and PDL cells compared to control and blood-coated samples. Moreover, there were significantly higher messenger ribonucleic acid levels of osteogenic differentiation markers, including collagen 1α1, alkaline phosphatase, and osteocalcin, in osteoblasts and PDL cells cultured on EMD-coated DFDBA particles at 3, 7, and 14 days. CONCLUSION The results suggest that the addition of EMD to DFDBA particles may influence periodontal regeneration by stimulating PDL cell and osteoblast proliferation and differentiation.

Long-term clinical, microbiological, and radiographic outcomes of Brånemark™ implants installed in augmented maxillary bone for fixed full-arch rehabilitation

PURPOSE The purpose of this study was to document the long-term outcome of Brånemark implants installed in augmented maxillary bone and to identify parameters that are associated with peri-implant bone level. MATERIAL AND METHODS Patients of a periodontal practice who had been referred to a maxillofacial surgeon for iliac crest bone grafting in the atrophic maxilla were retrospectively recruited. Five months following grafting, they received 7-8 turned Brånemark implants. Following submerged healing of another 5 months, implants were uncovered and restorative procedures for fixed rehabilitation were initiated 2-3 months thereafter. The primary outcome variable was bone level defined as the distance from the implant-abutment interface to the first visible bone-to-implant contact. Secondary outcome variables included plaque index, bleeding index, probing depth, and levels of 40 species in subgingival plaque samples as identified by means of checkerboard DNA-DNA hybridization. RESULTS Nine out of 16 patients (eight females, one male; mean age 59) with 71 implants agreed to come in for evaluation after on average 9 years (SD 4; range 3-13) of function. One implant was deemed mobile at the time of inspection. Clinical conditions were acceptable with 11% of the implants showing pockets ≥ 5 mm. Periodontopathogens were encountered frequently and in high numbers. Clinical parameters and bacterial levels were highly patient dependent. The mean bone level was 2.30 mm (SD 1.53; range 0.00-6.95), with 23% of the implants demonstrating advanced resorption (bone level > 3 mm). Regression analysis showed a significant association of the patient (p < .001) and plaque index (p = .007) with bone level. CONCLUSIONS The long-term outcome of Brånemark implants installed in iliac crest-augmented maxillary bone is acceptable; however, advanced peri-implant bone loss is rather common and indicative of graft resorption. This phenomenon is patient dependent and seems also associated with oral hygiene.

DensiProbe Spine: an intraoperative measurement of bone quality in spinal instrumentation. A clinical feasibility study

BACKGROUND CONTEXT A new device, DensiProbe, has been developed to provide surgeons with intraoperative information about bone strength by measuring the peak breakaway torque. In cases of low bone quality, the treatment can be adapted to the patient's condition, for example, by improving screw-anchorage with augmentation techniques. PURPOSE The objective of this study was to investigate the feasibility of DensiProbe Spine in patients undergoing transpedicular fixation. STUDY DESIGN Prospective feasibility study on consecutive patients. PATIENT SAMPLE Fourteen women and 16 men were included in this study. OUTCOME MEASURES Local and general bone quality. METHODS These consecutive patients scheduled for transpedicular fixation were evaluated for bone mineral density (BMD), which was measured globally by dual-energy X-ray absorptiometry and locally via biopsies using quantitative microcomputed tomography. The breakaway torque force within the vertebral body was assessed intraoperatively via the transpedicular approach with the DensiProbe Spine. The results were correlated with the areal BMD at the lumbar spine and the local volumetric BMD (vBMD) and a subjective impression of bone strength. The feasibility of the method was evaluated, and the clinical and radiological performance was evaluated over a 1-year follow-up. This study was funded by an AO Spine research grant; DensiProbe was developed at the AO Research Institute Davos, Switzerland; the AO Foundation is owner of the intellectual property rights. RESULTS In 30 patients, 69 vertebral levels were examined. The breakaway torque consistently correlated with an experienced surgeon's quantified impression of resistance as well as with vBMD of the same vertebra. Beyond a marginal prolongation of surgery time, no adverse events related to the usage of the device were observed. CONCLUSIONS The intraoperative transpedicular measurement of the peak breakaway torque was technically feasible, safe, and reliably predictive of local vBMD during dorsal spinal instrumentations in a clinical setting. Larger studies are needed to define specific thresholds that indicate a need for the augmentation or instrumentation of additional levels.

Bone conduction in Thiel-embalmed cadaver heads

INTRODUCTION Sound can reach the inner ear via at least two different pathways: air conduction and bone conduction (BC). BC hearing is used clinically for diagnostic purposes and for BC hearing aids. Research on the motion of the human middle ear in response to BC stimulation is typically conducted using cadaver models. We evaluated middle ear motion of Thiel-embalmed whole-head specimens in terms of linearity, reproducibility, and consistency with the reported middle ear motion of living subjects, fresh cadaveric temporal bones, and whole-heads embalmed with a Non-Thiel solution of salts. METHODS We used laser Doppler vibrometry to measure the displacement of the skull, the umbo, the cochlear promontory, the stapes, and the round window in seven ears from four human whole-head specimens embalmed according to Thiel's method. The ears were stimulated with a Baha(®) implanted behind the auricle. RESULTS The Thiel model shows promontory velocity similar to that reported in the literature for whole-heads embalmed with a Non-Thiel solution of salts (0- to 7-dB difference). The Thiel heads' relative velocity of the stapes with respect to the promontory was similar to that of fresh cadaver temporal bones (0- to 4-dB difference). The velocity of the umbo was comparable in Thiel-embalmed heads and living subjects (0- to 10-dB difference). The skull and all middle ear elements measured responded linearly to different stimulation levels, with an average difference less than 1 dB. The variability of repeated measurements for both short- (2 h; 4 dB) and long-term (4-16 weeks; 6 dB) repetitions in the same ear, and the difference between the two ears of the same donor (approximately 10 dB) were lower than the inter-individual difference (up to 25 dB). CONCLUSION Thiel-embalmed human whole-head specimens can be used as an alternative model for the study of human middle ear mechanics secondary to BC stimulation. At some frequencies, differences from living subjects must be considered.

Impact of Switching From Zidovudine to Tenofovir Disoproxil Fumarate on Bone Mineral Density and Markers of Bone Metabolism in Virologically Suppressed HIV-1 Infected Patients; A Substudy of the PREPARE Study

Context: In virologically suppressed, antiretroviral-treated patients, the effect of switching to tenofovir (TDF) on bone biomarkers compared to patients remaining on stable antiretroviral therapy is unknown. Methods: We examined bone biomarkers (osteocalcin [OC], procollagen type 1 amino-terminal propeptide, and C-terminal cross-linking telopeptide of type 1 collagen) and bone mineral density (BMD) over 48 weeks in virologically suppressed patients (HIV RNA < 50 copies/ml) randomized to switch to TDF/emtricitabine (FTC) or remain on first-line zidovudine (AZT)/lamivudine (3TC). PTH was also measured. Between-group differences in bone biomarkers and associations between change in bone biomarkers and BMD measures were assessed by Student's t tests, Pearson correlation, and multivariable linear regression, respectively. All data are expressed as mean (SD), unless otherwise specified. Results: Of 53 subjects (aged 46.0 y; 84.9% male; 75.5% Caucasian), 29 switched to TDF/FTC. There were reductions in total hip and lumbar spine BMD in those switching to TDF/FTC (total hip, TDF/FTC, −1.73 (2.76)% vs AZT/3TC, −0.39 (2.41)%; between-group P = .07; lumbar spine, TDF/FTC, −1.50 (3.49)% vs AZT/3TC, +0.25 (2.82)%; between-group P = .06), but they did not reach statistical significance. Greater declines in lumbar spine BMD correlated with greater increases in OC (r = −0.28; P = .05). The effect of TDF/FTC on bone biomarkers remained significant when adjusted for baseline biomarker levels, gender, and ethnicity. There was no difference in change in PTH levels over 48 weeks between treatment groups (between-group P = .23). All biomarkers increased significantly from weeks 0 to 48 in the switch group, with no significant change in those remaining on AZT/3TC (between-group, all biomarkers, P < .0001). Conclusion: A switch to TDF/FTC compared to remaining on a stable regimen is associated with increases in bone turnover that correlate with reductions in BMD, suggesting that TDF exposure directly affects bone metabolism in vivo.

Early changes in biochemical markers of bone formation during teriparatide therapy correlate with improvements in vertebral strength in men with glucocorticoid-induced osteoporosis

Summary Changes of the bone formation marker PINP correlated positively with improvements in vertebral strength in men with glucocorticoid-induced osteoporosis (GIO) who received 18-month treatment with teriparatide, but not with risedronate. These results support the use of PINP as a surrogate marker of bone strength in GIO patients treated with teriparatide. Introduction To investigate the correlations between biochemical markers of bone turnover and vertebral strength estimated by finite element analysis (FEA) in men with GIO. Methods A total of 92 men with GIO were included in an 18-month, randomized, open-label trial of teriparatide (20 μg/day, n = 45) and risedronate (35 mg/week, n = 47). High-resolution quantitative computed tomography images of the 12th thoracic vertebra obtained at baseline, 6 and 18 months were converted into digital nonlinear FE models and subjected to anterior bending, axial compression and torsion. Stiffness and strength were computed for each model and loading mode. Serum biochemical markers of bone formation (amino-terminal-propeptide of type I collagen [PINP]) and bone resorption (type I collagen cross-linked C-telopeptide degradation fragments [CTx]) were measured at baseline, 3 months, 6 months and 18 months. A mixed-model of repeated measures analysed changes from baseline and between-group differences. Spearman correlations assessed the relationship between changes from baseline of bone markers with FEA variables. Results PINP and CTx levels increased in the teriparatide group and decreased in the risedronate group. FEA-derived parameters increased in both groups, but were significantly higher at 18 months in the teriparatide group. Significant positive correlations were found between changes from baseline of PINP at 3, 6 and 18 months with changes in FE strength in the teriparatide-treated group, but not in the risedronate group. Conclusions Positive correlations between changes in a biochemical marker of bone formation and improvement of biomechanical properties support the use of PINP as a surrogate marker of bone strength in teriparatide-treated GIO patients.

Development of an ex vivo protocol to model bone fracture in laying hens resulting from collisions.

Fractures of the keel bone, a bone extending ventrally from the sternum, are a serious health and welfare problem in free range laying hens. Recent findings suggest that a major cause of keel damage within extensive systems is collisions with internal housing structures, though investigative efforts have been hindered by difficulties in examining mechanisms and likely influencing factors at the moment of fracture. The objectives of this study were to develop an ex vivo impact protocol to model bone fracture in hens caused by collision, to assess impact and bird-related factors influencing fracture occurrence and severity, and to identify correlations of mechanical and structural properties between different skeletal sites. We induced keel bone fractures in euthanized hens using a drop-weight impact tester able to generate a range of impact energies, producing fractures that replicate those commonly found in commercial settings. The results demonstrated that impact energies of a similar order to those expected in normal housing were able to produce fractures, and that greater collision energies resulted in an increased likelihood of fractures and of greater severity. Relationships were also seen with keel's lateral surface bone mineral density, and the peak reactive force (strength) at the base of the manubrial spine. Correlations were also identified between the keel and long bones with respect to both strength and bone mineral density. This is the first study able to relate impact and bone characteristics with keel bone fracture at the moment of collision. Greater understanding of these relationships will provide means to reduce levels of breakage and severity in commercial systems.

Reduced bone breakage and increased bone strength in free range laying hens fed omega-3 polyunsaturated fatty acid supplemented diets

INTRODUCTION The omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) are the immediate precursors to a number of important mediators of immunity, inflammation and bone function, with products of omega-6 generally thought to promote inflammation and favour bone resorption. Western diets generally provide a 10 to 20-fold deficit in omega-3 PUFAs compared with omega-6, and this is thought to have contributed to the marked rise in incidence of disorders of modern human societies, such as heart disease, colitis and perhaps osteoporosis. Many of our food production animals, fed on grains rich in omega-6, are also exposed to a dietary deficit in omega-3, with perhaps similar health consequences. Bone fragility due to osteoporotic changes in laying hens is a major economic and welfare problem, with our recent estimates of breakage rates indicating up to 95% of free range hens suffer breaks during lay. METHODS Free range hens housed in full scale commercial systems were provided diets supplemented with omega-3 alpha linolenic acid, and the skeletal benefits were investigated by comparison to standard diets rich in omega-6. RESULTS There was a significant 40-60% reduction in keel bone breakage rate, and a corresponding reduction in breakage severity in the omega-3 supplemented hens. There was significantly greater bone density and bone mineral content, alongside increases in total bone and trabecular volumes. The mechanical properties of the omega-3 supplemented hens were improved, with strength, energy to break and stiffness demonstrating significant increases. Alkaline phosphatase (an osteoblast marker) and tartrate-resistant acid phosphatase (an osteoclast marker) both showed significant increases with the omega-3 diets, indicating enhanced bone turnover. This was corroborated by the significantly lower levels of the mature collagen crosslinks, hydroxylysyl pyridinoline, lysyl pyridinoline and histidinohydroxy-lysinonorleucine, with a corresponding significant shift in the mature:immature crosslink ratio. CONCLUSIONS The improved skeletal health in laying hens corresponds to as many as 68million fewer hens suffering keel fractures in the EU each year. The biomechanical and biochemical evidence suggests that increased bone turnover has enhanced the bone mechanical properties, and that this may suggest potential benefits for human osteoporosis.