Jon J. Camp

Population‐Based Study of Age and Sex Differences in Bone Volumetric Density, Size, Geometry, and Structure at Different Skeletal Sites

In a population‐based, cross‐sectional study, we assessed age‐ and sex‐specific changes in bone structure by QCT. Over life, the cross‐sectional area of the vertebrae and proximal femur increased by ∼15% in both sexes, whereas vBMD at these sites decreased by 39–55% and 34–46%, respectively, with greater decreases in women than in men.

A Population-Based Assessment of Rates of Bone Loss at Multiple Skeletal Sites : Evidence for Substantial Trabecular Bone Loss in Young Adult Women and Men

Using QCT, we made a longitudinal, population‐based assessment of rates of bone loss over life at the distal radius, distal tibia, and lumbar spine. Cortical bone loss began in perimenopause in women and later in life in men. In contrast, trabecular bone loss began in young adulthood in both sexes.

Structural Determinants of Vertebral Fracture Risk

Vertebral fractures are more strongly associated with specific bone density, structure, and strength parameters than with areal BMD, but all of these variables are correlated.

Defects in Mitochondrial Dynamics and Metabolomic Signatures of Evolving Energetic Stress in Mouse Models of Familial Alzheimer's Disease

Background The identification of early mechanisms underlying Alzheimers Disease (AD) and associated biomarkers could advance development of new therapies and improve monitoring and predicting of AD progression. Mitochondrial dysfunction has been suggested to underlie AD pathophysiology, however, no comprehensive study exists that evaluates the effect of different familial AD (FAD) mutations on mitochondrial function, dynamics, and brain energetics. Methods and Findings We characterized early mitochondrial dysfunction and metabolomic signatures of energetic stress in three commonly used transgenic mouse models of FAD. Assessment of mitochondrial motility, distribution, dynamics, morphology, and metabolomic profiling revealed the specific effect of each FAD mutation on the development of mitochondrial stress and dysfunction. Inhibition of mitochondrial trafficking was characteristic for embryonic neurons from mice expressing mutant human presenilin 1, PS1(M146L) and the double mutation of human amyloid precursor protein APP(Tg2576) and PS1(M146L) contributing to the increased susceptibility of neurons to excitotoxic cell death. Significant changes in mitochondrial morphology were detected in APP and APP/PS1 mice. All three FAD models demonstrated a loss of the integrity of synaptic mitochondria and energy production. Metabolomic profiling revealed mutation-specific changes in the levels of metabolites reflecting altered energy metabolism and mitochondrial dysfunction in brains of FAD mice. Metabolic biomarkers adequately reflected gender differences similar to that reported for AD patients and correlated well with the biomarkers currently used for diagnosis in humans. Conclusions Mutation-specific alterations in mitochondrial dynamics, morphology and function in FAD mice occurred prior to the onset of memory and neurological phenotype and before the formation of amyloid deposits. Metabolomic signatures of mitochondrial stress and altered energy metabolism indicated alterations in nucleotide, Krebs cycle, energy transfer, carbohydrate, neurotransmitter, and amino acid metabolic pathways. Mitochondrial dysfunction, therefore, is an underlying event in AD progression, and FAD mouse models provide valuable tools to study early molecular mechanisms implicated in AD.

Age- and sex-specific differences in the factor of risk for vertebral fracture: a population-based study using QCT.

We used QCT scans obtained in 687 men and women, 21–97 years of age, to estimate the factor of risk for vertebral fracture, Φvert, defined as the ratio of spinal loading to vertebral strength. With age, vertebral strength declined and Φvert increased significantly more in women than men. Age‐ and sex‐specific differences in Φvert closely resembled previously reported vertebral fracture incidence.

Relationship of Volumetric BMD and Structural Parameters at Different Skeletal Sites to Sex Steroid Levels in Men

In a population‐based, cross‐sectional study, we related age‐associated changes in vBMD and in bone structural parameters to circulating bioavailable estradiol and testosterone levels in men. Associations between these bone mass/structural parameters and sex steroid levels were progressively stronger with age. Our previously postulated “threshold” for skeletal estrogen deficiency was most evident at cortical sites.

A Bone Structural Basis for Fracture Risk in Diabetes

CONTEXT Elevated areal bone mineral density (aBMD) in type 2 diabetes mellitus is inconsistent with increased fracture risk at some skeletal sites. OBJECTIVES Because aBMD is an imperfect surrogate for bone strength, we assessed bone structure and strength more directly using quantitative computed tomography. DESIGN Diabetic and nondiabetic subjects were evaluated in a cross-sectional study. SETTING Subjects were recruited from a random sample of the Rochester, MN, population. PARTICIPANTS Forty-nine subjects (28 women and 21 men) with type 2 diabetes were compared with age- and sex-matched nondiabetic controls. MAIN OUTCOME MEASUREMENTS We measured bone geometry, strength, and volumetric BMD (vBMD) at the hip, spine, and wrist, along with hip aBMD, using central and peripheral quantitative computed tomography and estimated bone load to bone strength ratios at each site. RESULTS Adjusted for differences in body mass index between cases and controls (29.8 vs. 27.6), hip aBMD was greater in diabetic subjects, but this was accounted for by greater trabecular vBMD. Cortical vBMD was similar in the two groups, as was bone cross-sectional area and cortical thickness. Bone strength measures were generally better in diabetic subjects, but bone loads were higher from their greater weight. Consequently, load to strength ratios (i.e. factor-of-risk) were similar. CONCLUSIONS Patients with type 2 diabetes enjoy little benefit from elevated aBMD in terms of improved bone load to strength ratios. With no deficit in bone density, the rationale for antiresorptive therapy in diabetic patients is uncertain, but potential adverse effects of diabetes on bone quality need more study.

Population-based analysis of the relationship of whole bone strength indices and fall-related loads to age- and sex-specific patterns of hip and wrist fractures

In an age‐ and sex‐stratified population sample (n = 700), we estimated fall‐related loads and bone strength indices at the UDR and FN. These load/strength ratios more closely simulated patterns of wrist and hip fractures occurring in the same population than did measurement of vBMD.

Relation of vertebral deformities to bone density, structure, and strength.

Because they are not reliably discriminated by areal bone mineral density (aBMD) measurements, it is unclear whether minimal vertebral deformities represent early osteoporotic fractures. To address this, we compared 90 postmenopausal women with no deformity (controls) with 142 women with one or more semiquantitative grade 1 (mild) deformities and 51 women with any grade 2–3 (moderate/severe) deformities. aBMD was measured by dual‐energy X‐ray absorptiometry (DXA), lumbar spine volumetric bone mineral density (vBMD) and geometry by quantitative computed tomography (QCT), bone microstructure by high‐resolution peripheral QCT at the radius (HRpQCT), and vertebral compressive strength and load‐to‐strength ratio by finite‐element analysis (FEA) of lumbar spine QCT images. Compared with controls, women with grade 1 deformities had significantly worse values for many bone density, structure, and strength parameters, although deficits all were much worse for the women with grade 2–3 deformities. Likewise, these skeletal parameters were more strongly associated with moderate to severe than with mild deformities by age‐adjusted logistic regression. Nonetheless, grade 1 vertebral deformities were significantly associated with four of the five main variable categories assessed: bone density (lumbar spine vBMD), bone geometry (vertebral apparent cortical thickness), bone strength (overall vertebral compressive strength by FEA), and load‐to‐strength ratio (45‐degree forward bending ÷ vertebral compressive strength). Thus significantly impaired bone density, structure, and strength compared with controls indicate that many grade 1 deformities do represent early osteoporotic fractures, with corresponding implications for clinical decision making.

PUBOPERINEALES: MUSCULAR BOUNDARIES OF THE MALE UROGENITAL HIATUS IN 3D FROM MAGNETIC RESONANCE IMAGING

PURPOSE The aims of this report are 1) to extend our previous two-dimensional magnetic resonance imaging study to create a three-dimensional image of the pelvic floor, including the puboperinealis, the most anteromedial component of the levator ani; 2) to clarify the historical controversy about this particular component of the levator ani; and 3) to present clinical implications of this muscle with respect to urinary continence and radical prostatectomy. MATERIALS AND METHODS We reused the axial magnetic resonance imaging series from 1 of 15 men in a previous series. Analyze AVWTM allowed creation of three-dimensional images. Further, a movie clip of all three-dimensional images was developed and placed at the manuscript-dedicated Web site: http://www.mayo. edu/ppmovie/pp.html. RESULTS Our three-dimensional images show how the puboperinealis portion of the levator ani flanks the urethra as it courses from the pubis to its insertion in the perineal body. CONCLUSIONS The puboperinealis corresponds to muscles previously designated as the levator prostatae, Wilsons muscle, pubourethralis, and levator urethrae, among others. The images suggest that the puboperinealis is the muscle most responsible for the quick stop phenomenon of urination in the male. Our study supports the suggestion that weakening of the puboperinealis by transection, traction injury, or denervation may affect urinary continence after radical prostatectomy.