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All sourcesNASA NTRSDOE OSTI
NASA NTRS1988

Use of diphosphonates to correct disorders in calcium metabolism and mineral composition of bone tissue with 60-day hypokinesia in rats

Compounds of the diphosphonate group suppress bone resorption and bone tissue metabolism, from which it was assumed that they can be used for the prevention of osteoporosis and disorders of calcium homeostasis in humans during space flight. Two compounds of this group were used for preventive purposes in 60 day hypokinesia in rats. The results showed that diphosphonates have a marked effect on calcium metabolism and the condition of the bone tissues under conditions of long term hypokinesia: they reduce the content of ionized calcium in blood, delay the loss of calcium and phosphorus by the bone tissue, and to a considerable degree prevent reduction of bone density. This confirms the possibility of using compounds of this group for correcting and preventing changes of bone tissue and mineral metabolism during long term hypokinesia.

Morukov, B. V.↗
NASA NTRS1989

Determinants of bone density among athletes engaged in weight-bearing and non-weight-bearing activity

The effect of weight bearing activity on the bone density was investigated in athletes by comparing the measures of bone density of athletes engaged in weight-training programs with those of polo players and nonexercising subjects. All subjects had measurements of spinal trabecular and integral bone density by quantitative tomography, as well as determinations of hip bone density by dual photon absorptiometry. Results confirmed previous findings by Block et al. (1987) of significantly greater bone density among highly trained athletes compared with nonexercising subjects of similar age. Results also indicated that athletes engaged in non-weight-bearing forms of rigorous exercise had greater levels of bone density. However, as the participants in this study were exceptional athletes, engaged in a strenuous sport with both aerobic and heavy resistance components, a confirmation of these data is needed, using larger samples of individuals.

Block, Jon E.↗
NASA NTRS2000

Calcium and Bone Homeostasis During 4-6 Months Space Flight

Bone and calcium homeostasis are altered by weightlessness. We previously reported calcium studies on three subjects from the first joint US/Russian mission to Mir. We report here data on an additional three male subjects, whose stays on Mir were 4 (n= 1) and 6 (n=2) mos. Data were collected before, during, and after the missions. Inflight studies were conducted at 2-3 mos. Endocrine and biochemical indices were measured, along with 3-wk calcium tracer studies. Percent differences are reported compared to preflight. Ionized calcium was unchanged (2.8 +/-2.1 %) during flight. Calcium absorption was variable inflight, but was decreased after landing. Vitamin D stores were decreased 35 +/-24% inflight, similar to previous reports. Serum PTH was decreased 59 +/-9% during flight (greater than we previously reported), while 1,25(OH)(sub 2)-Vitamin D was decreased in 2 of 3 subjects. Markers of bone resorption (e.g., crosslinks) were increased in all subjects. Bone-specific alkaline phosphatase was decreased (n=1) or unchanged (n=2), while osteocalcin was decreased 34 +/-23%. Previously presented data showed that inflight bone loss is associated with increased resorption and unchanged/decreased formation. The data reported here support these earlier findings. These studies will help to extend our understanding of space flight-induced bone loss, and of bone loss associated with diseases such as osteoporosis or paralysis.

Smith, Scott M.↗
NASA NTRS2000

Overexpression of Human Bone Alkaline Phosphatase in Pichia Pastoris

The Pichiapastoris expression system was utilized to produce functionally active human bone alkaline phosphatase in gram quantities. Bone alkaline phosphatase is a key enzyme in bone formation and biomineralization, yet important questions about its structural chemistry and interactions with other cellular enzymes in mineralizing tissues remain unanswered. A soluble form of human bone alkaline phosphatase was constructed by deletion of the 25 amino acid hydrophobic C-terminal region of the encoding cDNA and inserted into the X-33 Pichiapastoris strain. An overexpression system was developed in shake flasks and converted to large-scale fermentation. Alkaline phosphatase was secreted into the medium to a level of 32mgAL when cultured in shake flasks. Enzyme activity was 12U/mg measured by a spectrophotometric assay. Fermentation yielded 880mgAL with enzymatic activity of 968U/mg. Gel electrophoresis analysis indicates that greater than 50% of the total protein in the fermentation is alkaline phosphatase. A purification scheme has been developed using ammonium sulfate precipitation followed by hydrophobic interaction chromatography. We are currently screening crystallization conditions of the purified recombinant protein for subsequent X-ray diffraction analyses. Structural data should provide additional information on the role of alkaline phosphatase in normal bone mineralization and in certain bone mineralization anomalies.

Karr, Laurel↗
NASA NTRS1996

Determination of Small Animal Long Bone Properties Using Densitometry

Assessment of bone structural property changes due to loading regimens or pharmacological treatment typically requires destructive mechanical testing and sectioning. Our group has accurately and non-destructively estimated three dimensional cross-sectional areal properties (principal moments of inertia, Imax and Imin, and principal angle, Theta) of human cadaver long bones from pixel-by-pixel analysis of three non-coplanar densitometry scans. Because the scanner beam width is on the order of typical small animal diapbyseal diameters, applying this technique to high-resolution scans of rat long bones necessitates additional processing to minimize errors induced by beam smearing, such as dependence on sample orientation and overestimation of Imax and Imin. We hypothesized that these errors are correctable by digital image processing of the raw scan data. In all cases, four scans, using only the low energy data (Hologic QDR-1000W, small animal mode), are averaged to increase image signal-to-noise ratio. Raw scans are additionally processed by interpolation, deconvolution by a filter derived from scanner beam characteristics, and masking using a variable threshold based on image dynamic range. To assess accuracy, we scanned an aluminum step phantom at 12 orientations over a range of 180 deg about the longitudinal axis, in 15 deg increments. The phantom dimensions (2.5, 3.1, 3.8 mm x 4.4 mm; Imin/Imax: 0.33-0.74) were comparable to the dimensions of a rat femur which was also scanned. Cross-sectional properties were determined at 0.25 mm increments along the length of the phantom and femur. The table shows average error (+/- SD) from theory of Imax, Imin, and Theta) over the 12 orientations, calculated from raw and fully processed phantom images, as well as standard deviations about the mean for the femur scans. Processing of phantom scans increased agreement with theory, indicating improved accuracy. Smaller standard deviations with processing indicate increased precision and repeatability. Standard deviations for the femur are consistent with those of the phantom. We conclude that in conjunction with digital image enhancement, densitometry scans are suitable for non-destructive determination of areal properties of small animal bones of comparable size to our phantom, allowing prediction of Imax and Imin within 2.5% and Theta within a fraction of a degree. This method represents a considerable extension of current methods of analyzing bone tissue distribution in small animal bones.

Breit, Gregory A.↗
NASA NTRS2003

Non-Invasive Investigation of Bone Adaptation in Humans to Cumulative Daily Mechanical Loading

The goal of our research is to better understand the functional relationship between cumulative daily skeletal loading generated by daily activity and the regulation of bone density and bone structure. We have proposed the calcaneus and tibia as useful model bone sites loaded by internal forces in equilibrium with the ground reaction force during gait. The daily history of the ground reaction force is a good relative measure of daily lower limb and calcaneal loading that can be compared to bone density and structure of the calcaneus and cross-sectional geometry of the tibia and fibula. Over the past several years, we have developed image-processing technologies to improve our ability to measure bone density and structure in the calcaneus and lower leg non-invasively with computed tomography and bone densitometry, or DXA. The objective of our current research effort is to determine the accuracy and precision of our CT and DXA image processing methods.

Whalen, Robert↗
NASA NTRS2002

Leptin regulates bone formation via the sympathetic nervous system

We previously showed that leptin inhibits bone formation by an undefined mechanism. Here, we show that hypothalamic leptin-dependent antiosteogenic and anorexigenic networks differ, and that the peripheral mediators of leptin antiosteogenic function appear to be neuronal. Neuropeptides mediating leptin anorexigenic function do not affect bone formation. Leptin deficiency results in low sympathetic tone, and genetic or pharmacological ablation of adrenergic signaling leads to a leptin-resistant high bone mass. beta-adrenergic receptors on osteoblasts regulate their proliferation, and a beta-adrenergic agonist decreases bone mass in leptin-deficient and wild-type mice while a beta-adrenergic antagonist increases bone mass in wild-type and ovariectomized mice. None of these manipulations affects body weight. This study demonstrates a leptin-dependent neuronal regulation of bone formation with potential therapeutic implications for osteoporosis.

NASA Discipline Regulatory Physiology↗
NASA NTRS2004

Biophotonics and Bone Biology

One of the more-serious side effects of extended space flight is an accelerated bone loss [Bioastronautics Critical Path Roadmap, http://research.hq.nasa.gov/code_u/bcpr/index.cfm]. Rates of bone loss are highest in the weight-bearing bones of the hip and spine regions, and the average rate of bone loss as measured by bone mineral density measurements is around 1.2% per month for persons in a microgravity environment. It shows that an extrapolation of the microgravity induced bone loss rates to longer time scales, such as a 2.5 year round-trip to Mars (6 months out at 0 g, 1.5 year stay on Mars at 0.38 g, 6 months back at 0 g), could severely compromise the skeletal system of such a person.

Zimmerli, Gregory↗
NASA NTRS2003

Effect of High Impact or Non-impact Loading Activity on Bone Bending Stiffness and Mineral Density

Material properties of conical bone, including mineral density (BMD) and its geometry is closely related to its load-carrying capacity. These two primary components determine the strength of conical bone. High impact loading involving acceleration and deceleration movements used in gymnastics induce higher BMD of the affected bone compared to the non-impact acceleration and deceleration movements used in swimming. Study of these two groups of athletes on bone bending stiffness has not been reported. The purpose of this study was to compare differences in bone bending stiffness and BMD between competitive female synchronized swimmers and female gymnasts. Thirteen world class female synchronized swimmers (SYN) and 8 female gymnasts (GYM), mean age 21 +/- 2.9 yr. were recruited for this study. We used a mechanical response tissue analyzer (Gaitscan, NJ) to calculate EI, where E is Young's modulus of elasticity and I is the cross-sectional moment of inertia. EI was obtained from tissue response to a vibration probe placed directly on the skin of the mid-region of tibia and ulna. BMD of the heel and wrist were measured with a probe densitometer (PIXI, Lunor, WI). The SYN were taller than (p < 0.05) the GYM but weighed the same as the GYM. EI obtained from tibia and ulna of the SYN (291 +/- 159 and 41 +/- 19.4, respectively) were not significantly different from thc GYM (285 +/- 140 and 44 +/- 18.3, respectively). BMD of the heel and wrist in GYM were higher than in SYN (p < 0.001). High impact weight-bearing activities promote similar bone strength but greater BMD response than non-impact activities performed in a buoyant environment.

Liang, Michael T. C.↗
NASA NTRS2007

Artificial Gravity as a Bone Loss Countermeasure in Simulated Weightlessness

The impact of microgravity on the human body is a significant concern for space travelers. We report here initial results from a pilot study designed to explore the utility of artificial gravity (AG) as a countermeasure to the effects of microgravity, specifically to bone loss. After an initial phase of adaptation and testing, 15 male subjects underwent 21 days of 6 head-down bed rest to simulate the deconditioning associated with space flight. Eight of the subjects underwent 1 h of centrifugation (AG, 1 gz at the heart, 2.5 gz at the feet) each day for 21 days, while 7 of the subjects served as untreated controls (CN). Blood and urine were collected before, during, and after bed rest for bone marker determinations. At this point, preliminary data are available on the first 8 subjects (6 AG, and 2 CN). Comparing the last week of bed rest to before bed rest, urinary excretion of the bone resorption marker n-telopeptide increased 95 plus or minus 59% (mean plus or minus SD) in CN but only 32 plus or minus 26% in the AG group. Similar results were found for another resorption marker, helical peptide (increased 57 plus or minus 0% and 35 plus or minus 13% in CN and AG respectively). Bone-specific alkaline phosphatase, a bone formation marker, did not change during bed rest. At this point, sample analyses are continuing, including calcium tracer kinetic studies. These initial data demonstrate the potential effectiveness of short-radius, intermittent AG as a countermeasure to the bone deconditioning that occurs during bed rest.

Smith, S. M.↗
NASA NTRS2009

Using the Enhanced Daily Load Stimulus Model to Quantify the Mechanical Load and Bone Mineral Density Changes Experienced by Crew Members on the International Space Station

Despite the use of exercise countermeasures during long-duration space missions, bone mineral density (BMD) and predicted bone strength of astronauts continue to show decreases in the lower extremities and spine. This site-specific bone adaptation is most likely caused by the effects of microgravity on the mechanical loading environment of the crew member. There is, therefore, a need to quantify the mechanical loading experienced on Earth and on-orbit to define the effect of a given "dose" of loading on bone homeostasis. Gene et al. recently proposed an enhanced DLS (EDLS) model that, when used with entire days of in-shoe forces, takes into account recently developed theories on the importance of factors such as saturation, recovery, and standing and their effects on the osteogenic response of bone to daily physical activity. This algorithm can also quantify the tinting and type of activity (sit/unload, stand, walk, run or other loaded activity) performed throughout the day. The purpose of the current study was to use in-shoe force measurements from entire typical work days on Earth and on-orbit in order to quantify the type and amount of loading experienced by crew members. The specific aim was to use these measurements as inputs into the EDLS model to determine activity timing/type and the mechanical "dose" imparted on the musculoskeletal system of crew members and relate this dose to changes in bone homeostasis.

Genc, K. O.↗
NASA NTRS2009

Human Research Program Human Health Countermeasures Element Bone and Muscle Risk Standing Review Panel (SRP)

The Bone and Muscle Risk Standing Review Panel (SRP) met at the NASA Johnson Space Center (JSC) on October 4-6, 2009 to discuss the areas of current and future research targeted by the Human Health Countermeasures (HHC) Element of the Human Research Program (HRP). Using evidence-based knowledge as a background for identified risks to astronaut health and performance, NASA had identified gaps in knowledge to address those risks. Ongoing and proposed tasks were presented to address the gaps. The charge to the Bone and Muscle Risk SRP was to review the gaps, evaluate whether the tasks addressed these gaps and to make recommendations to NASA s HRP Science Management Office regarding the Panel's review. The Bone and Muscle Risk SRP consisted of scientists who are experts in muscle, bone, or both and could evaluate the existing evidence with sufficient knowledge of the potential effects of long duration exposure to microgravity. More important, although expertise in basic science is important, the SRP was requested to evaluate the practicality of the proposed efforts in light of the realistic demands placed on the HRP. In short, all tasks presented in the Integrated Research Plan (IRP) should address specific questions related to the challenges faced by the astronauts as a result of prolonged exposure to microgravity. All tasks proposed to fill the gaps in knowledge should provide applied, translational data necessary to answer the specific questions. Several presentations were made to the SRP during the site visit and the SRP spent sufficient time to address the panel charge, either as a group or in separate sessions for the Bone and Muscle Risk subgroups. The SRP made a final debriefing to the HRP Program Scientist, Dr. John B. Charles, on October 6, 2009. Taking the evidence and identified risks as givens, the SRP concluded that 1) integration of information should lead to a more comprehensive approach to identifying the gaps, 2) not all tasks addressed the gaps as stated in the IRP, 3) better access should be given to the SRP to existing data to include in its review, and 4) there were some missing gaps and tasks. As a result the SRP recommended 1) combining certain gaps, which in some cases were addressed with identical tasks, 2) additional gaps and tasks to address some of the gaps, 3) deleting some gaps and tasks to better focus the efforts of NASA s HRP in prioritizing their efforts, and 4) prioritizing gaps to address significant issues needing resolution in the short term while maintaining an awareness of long-term goals. The SRP commended the efforts by the HHC Element to integrate knowledge gaps and design tasks to address the higher order questions. This integration did not apply to the Bone and Muscle Risk alone, but the musculoskeletal system as its functions integrate with issues in

Glowacki, Julie↗
NASA NTRS2004

Variations in Urine Calcium Isotope: Composition Reflect Changes in Bone Mineral Balance in Humans

Changes in bone mineral balance cause rapid and systematic changes in the calcium isotope composition of human urine. Urine from subjects in a 17 week bed rest study was analyzed for calcium isotopic composition. Comparison of isotopic data with measurements of bone mineral density and metabolic markers of bone metabolism indicates the calcium isotope composition of urine reflects changes in bone mineral balance. Urine calcium isotope composition probably is affected by both bone metabolism and renal processes. Calcium isotope. analysis of urine and other tissues may provide information on bone mineral balance that is in important respects better than that available from other techniques, and illustrates the usefulness of applying geochemical techniques to biomedical problems.

Skulan, Joseph↗
NASA NTRS2012

High Protein Intake Improves Insulin Sensitivity but Exacerbates Bone Resorption in Immobility (WISE Study)

Inactivity, like bed rest (BR), causes insulin resistance (IR) and bone loss even in healthy subjects. High protein intake seems to mitigate this IR but might exacerbate bone loss. We hypothesized that high protein intake (animal:vegetable protein ratio: 60:40), isocaloric, compared to the control group plus high potassium intake would prevent IR without affecting bone turnover. After a 20-day ambulatory adaptation to controlled confinement and diet, 16 women participated in a 60-day, 6 deg head-down-tilt BR and were assigned randomly to one of the two groups. Control subjects (CON, n=8) received 1g/kg body mass/d dietary protein. Nutrition subjects (NUT, n=8) received 1.45g/kg body mass/d dietary protein plus 7.2g branched chain amino acids per day during BR. All subjects received 1670 kcal/d. Bed rest decreased glucose disposal by 35% (p<0.05) in CON. Isocaloric high protein intake prevented insulin resistance, but exacerbated bed rest induced increase in bone resorption markers C-telopeptide (> 30%) and Ntelopeptide (>20%) (both: p<0.001). Bone formation markers were unaffected by high protein intake. We conclude from these results that high protein intake might positively affect glucose tolerance, but might also foster bone loss. Further long-duration studies are mandatory before high protein intake for diabetic patients, who have an increased fracture risk, might be recommended.

Heer, Martina↗
NASA NTRS2012

Late Effects of Heavy Ion Irradiation on Ex Vivo Osteoblastogenesis and Cancellous Bone Microarchitecture

Prolonged spaceflight causes degeneration of skeletal tissue with incomplete recovery even after return to Earth. We hypothesize that heavy ion irradiation, a component of Galactic Cosmic Radiation, damages osteoblast progenitors and may contribute to bone loss during long duration space travel beyond the protection of the Earth's magnetosphere. Male, 16 week old C57BL6/J mice were exposed to high LET (56 Fe, 600MeV) radiation using either low (5 or 10cGy) or high (50 or 200cGy) doses at the NASA Space Radiation Lab and were euthanized 3 - 4, 7, or 35 days later. Bone structure was quantified by microcomputed tomography (6.8 micron pixel size) and marrow cell redox assessed using membrane permeable, free radical sensitive fluorogenic dyes. To assess osteoblastogenesis, adherent marrow cells were cultured ex vivo, then mineralized nodule formation quantified by imaging and gene expression analyzed by RT PCR. Interestingly, 3 - 4 days post exposure, fluorogenic dyes that reflect cytoplasmic generation of reactive nitrogen/oxygen species (DAF FM Diacetate or CM H2DCFDA) revealed irradiation (50cGy) reduced free radical generation (20-45%) compared to sham irradiated controls. Alternatively, use of a dye showing relative specificity for mitochondrial superoxide generation (MitoSOX) revealed an 88% increase compared to controls. One week after exposure, reactive oxygen/nitrogen levels remained lower(24%) relative to sham irradiated controls. After one month, high dose irradiation (200 cGy) caused an 86% decrement in ex vivo nodule formation and a 16-31% decrement in bone volume to total volume and trabecular number (50, 200cGy) compared to controls. High dose irradiation (200cGy) up regulated expression of a late osteoblast marker (BGLAP) and select genes related to oxidative metabolism (Catalase) and DNA damage repair (Gadd45). In contrast, lower doses (5, 10cGy) did not affect bone structure or ex vivo nodule formation, but did down regulate iNOS by 0.54 - 0.58 fold. Thus, both low and high doses of heavy ion irradiation cause time dependent, adaptive changes in redox state within marrow cells but only high doses (50, 200cGy) inhibit osteoblastogenesis and cause cancellous bone loss. We conclude space radiation has the potential to cause persistent damage to bone marrow derived stem and progenitor cells for osteoblasts despite adaptive changes in cellular redox state.

Tran, Luan Hoang↗
NASA NTRS2009

Bone Remodeling Monitor

The impact of bone loss due to different mechanical loadings in microgravity is a major concern for astronauts upon reintroduction to gravitational forces in exploration missions to the Moon and Mars. it has been shown that astronauts not only lose bone at differing rates, with levels up to 2% per month, but each astronaut will respond to bone loss treatments differently. Pre- and post-flight imaging techniques and frozen urine samples for post-flight laboratory immunoassays To develop a novel, non-invasive, highly . sensitive, portable, intuitive, and low-powered device to measure bone resorption levels in 'real time' to provide rapid and Individualized feedback to maximize the efficacy of bone loss countermeasures 1. Collect urine specimen and analyze the level of bone resorption marker, DPD (deoxypridinoline) excreted. 2. Antibodies specific to DPD conjugated with nanoshells and mixed with specimen, the change in absorbance from agglutination is measured by an optical device. 3. The concentration of DPD is displayed and recorded on a PDA

Foucar, Charlie↗
NASA NTRS2014

Astronaut Bone Medical Standards Derived from Finite Element (FE) Models of QCT Scans from Population Studies

This work was accomplished in support of the Finite Element [FE] Strength Task Group, NASA Johnson Space Center [JSC], Houston, TX. This group was charged with the task of developing rules for using finite-element [FE] bone-strength measures to construct operating bands for bone health that are relevant to astronauts following exposure to spaceflight. FE modeling is a computational tool used by engineers to estimate the failure loads of complex structures. Recently, some engineers have used this tool to characterize the failure loads of the hip in population studies that also monitored fracture outcomes. A Directed Research Task was authorized in July, 2012 to investigate FE data from these population studies to derive these proposed standards of bone health as a function of age and gender. The proposed standards make use of an FE-based index that integrates multiple contributors to bone strength, an expanded evaluation that is critical after an astronaut is exposed to spaceflight. The current index of bone health used by NASA is the measurement of areal BMD. There was a concern voiced by a research and clinical advisory panel that the sole use of areal BMD would be insufficient to fully evaluate the effects of spaceflight on the hip. Hence, NASA may not have a full understanding of fracture risk, both during and after a mission, and may be poorly estimating in-flight countermeasure efficacy. The FE Strength Task Group - composed of principal investigators of the aforementioned population studies and of FE modelers -donated some of its population QCT data to estimate of hip bone strength by FE modeling for this specific purpose. Consequently, Human Health Countermeasures [HHC] has compiled a dataset of FE hip strengths, generated by a single FE modeling approach, from human subjects (approx.1060) with ages covering the age range of the astronauts. The dataset has been analyzed to generate a set of FE strength cutoffs for the following scenarios: a) Qualify an applicant for astronaut candidacy, b) Qualify an astronaut for a long-duration (LD) mission, c) Qualify a veteran LD astronaut for a second LD mission, and d) Establish a non-permissible, minimum hip strength following a given mission architecture. This abstract will present the FE-based standards accepted by the FE Strength Task Group for its recommendation to HHC in January 2015.

Sibonga, J. D.↗
NASA NTRS2016

Bone Turnover Does Not Reflect Skeletal Aging in Older Hispanic Men with Type 2 Diabetes

The paradox of fragility fracture in the presence of non-osteoporotic bone mineral density in older patients with type 2 diabetes mellitus (DM2) makes it difficult to clinically predict fracture in this vulnerable group. Serum osteocalcin (OC), a marker of bone turnover, increases with normal skeletal aging indicating risk of fracture. However, OC has been reported to be lower in patients with DM2. An inverse association between higher glycated hemoglobin levels (HbA1c) and lower serum OC in older DM2 patients triggered discussions encouraging further investigation. A key question to be answered is whether changes in glucose metabolism is responsible for bone metabolic changes, ultimately leading to increased risk of fragility fractures in DM2 patients. While these studies were conducted among Caucasian and Asian populations, this has not been studied in Hispanic populations who suffer from a higher prevalence of DM2. The Cameron County Hispanic Cohort (CCHC) in Texas is a homogeneous Hispanic cohort known to have high prevalence of DM2 (30%). Our preliminary data from this cohort reported OC levels lower than the suggested threshold for fragility fracture in post-menopausal women. We further investigated whether bone turnover in older CCHC adults with DM2 show a normal pattern of skeletal aging. Samples and data were obtained from a nested cohort of 68 (21 men and 47 women) Hispanic older adults (≥50 years) who had a diagnosis of DM2. Given high prevalence of uncontrolled DM2 in this cohort, we divided population into two groups: i) poor DM2 control with HbA1c level ≥8 (48% men and 38% women) and ii) good DM2 control with HbA1c level <8). A crosssectional analysis documented associations between serum OC and age adjusted HbA1c levels. There was no direct association between age and OC concentrations in our study. Higher HbA1c was associated with lower serum OC in men (odds ratio -6.5, 95% confidence interval -12.7 to - 0.3, p < 0.04). No significant associations were identified in women. Bone turnover in older Hispanic men with DM2 in our study does not reflect normal pattern of skeletal aging. It is unclear why similar results were not identified in women. We will continue to follow this cohort to investigate longitudinal trend of changes of bone turnover and its relationship with HbA1c in both men and women of this cohort.

Rianon, N.↗