Femoral neck cortical bone in female and male hip fracture cases: Differential contrasts in cortical width and sub-periosteal porosity in 112 cases and controls.

Objectives: To quantitate differences between cases of hip fracture and controls in cortical width around the mid-femoral neck in men and women.

Methods: Over 5 years, 64 (14 male) participants over age 55 (mean 79) years, who had never taken bone-active drugs and suffered intra-capsular hip fracture treated by arthroplasty, donated their routinely discarded distal intra-capsular femoral neck bone for histomorphometry. After embedding, complete femoral neck cross sections from the cut surface near the narrowest part of the neck were stained with von Kossa and cortical width was measured radially every 5 degrees of arc.

The fragile elderly hip: mechanisms associated with age-related loss of strength and toughness.

Every hip fracture begins with a microscopic crack, which enlarges explosively over microseconds. Most hip fractures in the elderly occur on falling from standing height, usually sideways or backwards. The typically moderate level of trauma very rarely causes fracture in younger people.

Fourier transform infrared imaging of femoral neck bone: reduced heterogeneity of mineral-to-matrix and carbonate-to-phosphate and more variable crystallinity in treatment-naive fracture cases compared with fracture-free controls.

After the age of 60 years, hip fracture risk strongly increases, but only a fifth of this increase is attributable to reduced bone mineral density (BMD, measured clinically). Changes in bone quality, specifically bone composition as measured by Fourier transform infrared spectroscopic imaging (FTIRI), also contribute to fracture risk. Here, FTIRI was applied to study the femoral neck and provide spatially derived information on its mineral and matrix properties in age-matched fractured and nonfractured bones.

Extracellular matrix mineralization promotes E11/gp38 glycoprotein expression and drives osteocytic differentiation.

Osteocytes are terminally differentiated osteoblasts which reside in a mineralized extracellular matrix (ECM). The factors that regulate this differentiation process are unknown. We have investigated whether ECM mineralization could promote osteocyte formation.

Osteocyte recruitment declines as the osteon fills in: interacting effects of osteocytic sclerostin and previous hip fracture on the size of cortical canals in the femoral neck.

There is little information on the distribution of osteocytes within the individual cortical osteon, but using direct 3-D imaging in a single subject, Hannah et al. found a gradient with a two-fold higher density of cells adjacent to the cement line compared to near the canal. Since a limiting factor for bone formation might be the availability of osteoblasts due to their recruitment as osteocytes, we studied distributions of osteonal osteocytes in frozen sections of the femoral neck cortex.

Patients with sclerosteosis and disease carriers: human models of the effect of sclerostin on bone turnover.

Sclerosteosis is a rare bone sclerosing dysplasia, caused by loss-of-function mutations in the SOST gene, encoding sclerostin, a negative regulator of bone formation. The purpose of this study was to determine how the lack of sclerostin affects bone turnover in patients with sclerosteosis and to assess whether sclerostin synthesis is decreased in carriers of the SOST mutation and, if so, to what extent this would affect their phenotype and bone formation. We measured sclerostin, procollagen type 1 amino-terminal propeptide (P1NP), and cross-linked C-telopeptide (CTX) in serum of 19 patients with sclerosteosis, 26 heterozygous carriers of the C69T SOST mutation, and 77 healthy controls.

Sclerostin and the regulation of bone formation: Effects in hip osteoarthritis and femoral neck fracture.

Remodeling imbalance in the elderly femoral neck can result in thin cortices and porosity predisposing to hip fracture. Hip osteoarthritis protects against intracapsular hip fracture. By secreting sclerostin, osteocytes may inhibit Wnt signaling and reduce bone formation by osteoblasts.

Changing structure of the femoral neck across the adult female lifespan.

The anatomic distribution of cortical and cancellous bone in the femoral neck may be critical in determining resistance to fracture. We investigated the effects of aging on femoral neck bone in women. In this cross-sectional study, we used clinical multidetector computed tomography (MDCT) of the hips to investigate aging effects in 100 female volunteers aged 20 to 90 years.

Femoral neck trabecular bone: loss with aging and role in preventing fracture.

Hip fracture risk rises 100- to 1000-fold over six decades of age, but only a minor part of this increase is explained by declining BMD. A potentially independent cause of fragility is cortical thinning predisposing to local crushing, in which bone tissue's material disintegrates at the microscopic level when compressed beyond its capacity to maintain integrity. Elastic instability or buckling of a much thinned cortex might alternatively occur under compression.

Genetic selection for fast growth generates bone architecture characterised by enhanced periosteal expansion and limited consolidation of the cortices but a diminution in the early responses to mechanical loading.

Bone strength is, in part, dependent on a mechanical input that regulates the (re)modelling of skeletal elements to an appropriate size and architecture to resist fracture during habitual use. The rate of longitudinal bone growth in juveniles can also affect fracture incidence in adulthood, suggesting an influence of growth rate on later bone quality. We have compared the effects of fast and slow growth on bone strength and architecture in the tibiotarsi of embryonic and juvenile birds.

Bone structure and remodelling in stroke patients: early effects of zoledronate.

Introduction: We have reported that after an acute stroke, intravenous zoledronate prevented bone loss in the hemiplegic hip. Participants from the trial also volunteered for trans-iliac bone biopsy, to assess the early effects of stroke and zoledronate on iliac bone remodelling.

Methods: Patients with acute stroke were randomly assigned to a single intravenous dose of zoledronate 4 mg or placebo within 5 weeks of stroke.

Increased longitudinal growth in rats on a silicon-depleted diet.

Silicon-deficiency studies in growing animals in the early 1970s reported stunted growth and profound defects in bone and other connective tissues. However, more recent attempts to replicate these findings have found mild alterations in bone metabolism without any adverse health effects. Thus the biological role of silicon remains unknown.

A single infusion of zoledronate prevents bone loss after stroke.

Background And Purpose: Stroke is a major risk factor for hip fracture. Patients with intermediate rather than severe or mild stroke deficits at the time of hospital discharge have the most fractures. This proof-of-concept study evaluated the efficacy of a single infusion of zoledronate, an intravenous bisphosphonate, in preserving hip bone density after stroke.

Infant growth influences proximal femoral geometry in adulthood.

Unlabelled: The relationship between early growth and adult femoral geometry has not been studied previously. In 333 adults, we were able to show that infant weight predicts femoral width and cross-sectional moment of inertia but not femoral neck length. These results support the hypothesis that growth in early life leads to persisting differences in proximal femoral geometry.

Reduced vitamin D in acute stroke.

Background And Purpose: Stroke leads to a reduction in bone mineral density, altered calcium homeostasis, and an increase in hip fractures. Vitamin D deficiency is well documented in long-term stroke survivors and is associated with post-stroke hip fractures. Less is known regarding levels in acute stroke.

Sclerostin is a delayed secreted product of osteocytes that inhibits bone formation.

Osteocytes are the most abundant cells in bone and are ideally located to influence bone turnover through their syncytial relationship with surface bone cells. Osteocyte-derived signals have remained largely enigmatic, but it was recently reported that human osteocytes secrete sclerostin, an inhibitor of bone formation. Absent sclerostin protein results in the high bone mass clinical disorder sclerosteosis.

Relation between age, femoral neck cortical stability, and hip fracture risk.

Background: Hip fracture risk rises 100 to 1000-fold over 60 years of ageing. Loss of resistance to bending is not a major feature of normal ageing of the femoral neck. Another cause of fragility is local buckling or elastic instability.

Osteocytic expression of constitutive NO synthase isoforms in the femoral neck cortex: a case-control study of intracapsular hip fracture.

Unlabelled: NO is an osteocytic signaling molecule that can inhibit osteoclasts. The NO synthases eNOS and nNOS were expressed by >50% of osteonal osteocytes in controls. Hip fracture cases showed +NOS osteocytes only in deep osteonal bone, and 25-35% reduced expression overall.

Bone mineralization density and femoral neck fragility.

The traditional view of osteoporotic fractures is that they result from a reduction in bone mass combined with alterations in the micro-architecture. Apart from the effects of bone remodeling, the material properties of the remaining bone are thought to be unaffected. To test this, we compared the degree of matrix mineralization in femoral neck biopsies taken from cases of intracapsular hip fracture with age- and sex-matched postmortem controls.

Ghrelin and des-octanoyl ghrelin promote adipogenesis directly in vivo by a mechanism independent of the type 1a growth hormone secretagogue receptor.

Ghrelin promotes fat accumulation, despite potent stimulation of the lipolytic hormone, GH. The function of the major circulating isoform of ghrelin, des-octanoyl ghrelin, is unclear, because it does not activate the GH secretagogue receptor (GHS-R1a) and lacks the endocrine activities of ghrelin. We have now addressed these issues by infusing ghrelin, des-octanoyl ghrelin, or synthetic GHS-R1a agonists into three rat models with moderate, severe, or total GH deficiency.

Effects of gender, anthropometric variables, and aging on the evolution of hip strength in men and women aged over 65.

Although gender differences in fall rates may partly explain the higher prevalence of fractures in elderly women than men, male bones may also be intrinsically stronger or suffer less structural degradation with age than those of women. We used hip structural analysis (HSA) to study gender differences in hip geometry and bone mineral density (BMD) as they evolved over time in elderly white men and women with the aim of identifying candidate biological pathways leading to heightened risk of hip fracture. We recruited 443 women and 439 men aged 67-79 years from a diet and cancer prospective population-based cohort study to a study of hip bone loss.

Bone marrow adipocytes: a neglected target tissue for growth hormone.

Bone marrow (BM) contains numerous adipocytes. These share a common precursor with osteoblasts and chondrocytes, but their function is unknown. It is unclear what regulates the differentiation of these three different cell types, though their subsequent metabolic activity is under hormonal regulation.