Tracking of spaceflight-induced bone remodeling reveals a limited time frame for recovery of resorption sites in humans.

Mechanical unloading causes bone loss, but it remains unclear whether disuse-induced changes to bone microstructure are permanent or can be recovered upon reloading. We examined bone loss and recovery in 17 astronauts using time-lapsed high-resolution peripheral quantitative computed tomography and biochemical markers to determine whether disuse-induced changes are permanent. During 6 months in microgravity, resorption was threefold higher than formation.

The Case for Bisphosphonate Use in Astronauts Flying Long-Duration Missions.

Changes in the structure of bone can occur in space as an adaptive response to microgravity and on Earth due to the adaptive effects to exercise, to the aging of bone cells, or to prolonged disuse. Knowledge of cell-mediated bone remodeling on Earth informs our understanding of bone tissue changes in space and whether these skeletal changes might increase the risk for fractures or premature osteoporosis in astronauts. Comparisons of skeletal health between astronauts and aging humans, however, may be both informative and misleading.

Effects of exercise countermeasures on multisystem function in long duration spaceflight astronauts.

Exercise training is a key countermeasure used to offset spaceflight-induced multisystem deconditioning. Here, we evaluated the effects of exercise countermeasures on multisystem function in a large cohort (N = 46) of astronauts on long-duration spaceflight missions. We found that during 178 ± 48 d of spaceflight, ~600 min/wk of aerobic and resistance exercise did not fully protect against multisystem deconditioning.

Human Health during Space Travel: State-of-the-Art Review.

The field of human space travel is in the midst of a dramatic revolution. Upcoming missions are looking to push the boundaries of space travel, with plans to travel for longer distances and durations than ever before. Both the National Aeronautics and Space Administration (NASA) and several commercial space companies (e.

Incomplete recovery of bone strength and trabecular microarchitecture at the distal tibia 1 year after return from long duration spaceflight.

Determining the extent of bone recovery after prolonged spaceflight is important for understanding risks to astronaut long-term skeletal health. We examined bone strength, density, and microarchitecture in seventeen astronauts (14 males; mean 47 years) using high-resolution peripheral quantitative computed tomography (HR-pQCT; 61 μm). We imaged the tibia and radius before spaceflight, at return to Earth, and after 6- and 12-months recovery and assessed biomarkers of bone turnover and exercise.

Relations Between Bone Quantity, Microarchitecture, and Collagen Cross-links on Mechanics Following In Vivo Irradiation in Mice.

Humans are exposed to ionizing radiation via spaceflight or cancer radiotherapy, and exposure from radiotherapy is known to increase risk of skeletal fractures. Although irradiation can reduce trabecular bone mass, alter trabecular microarchitecture, and increase collagen cross-linking, the relative contributions of these effects to any loss of mechanical integrity remain unclear. To provide insight, while addressing both the monotonic strength and cyclic-loading fatigue life, we conducted total-body, acute, gamma-irradiation experiments on skeletally mature (17-week-old) C57BL/6J male mice ( = 84).

Pre-flight exercise and bone metabolism predict unloading-induced bone loss due to spaceflight.

Objectives: Bone loss remains a primary health concern for astronauts, despite in-flight exercise. We examined changes in bone microarchitecture, density and strength before and after long-duration spaceflight in relation to biochemical markers of bone turnover and exercise.

Methods: Seventeen astronauts had their distal tibiae and radii imaged before and after space missions to the International Space Station using high-resolution peripheral quantitative CT.

Use of Quantitative Computed Tomography to Assess for Clinically-relevant Skeletal Effects of Prolonged Spaceflight on Astronaut Hips.

Introduction: In 2010, experts in osteoporosis and bone densitometry were convened by the Space Life Sciences Directorate at NASA Johnson Space Center to identify a skeletal outcome in astronauts after spaceflight that would require a clinical response to address fracture risk. After reviewing astronaut data, experts expressed concern over discordant patterns in loss and recovery of bone mineral density (BMD) after spaceflight as monitored by dual-energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT). The pilot study described herein demonstrates the use of QCT to evaluate absence of recovery in hip trabecular BMD by QCT as an indicator of a clinically actionable response.

Hip load capacity cut-points for Astronaut Skeletal Health NASA Finite Element Strength Task Group Recommendations.

Concerns raised at a 2010 Bone Summit held for National Aeronautics and Space Administration Johnson Space Center led experts in finite element (FE) modeling for hip fracture prediction to propose including hip load capacity in the standards for astronaut skeletal health. The current standards for bone are based upon areal bone mineral density (aBMD) measurements by dual X-ray absorptiometry (DXA) and an adaptation of aBMD cut-points for fragility fractures. Task Group members recommended (i) a minimum permissible outcome limit (POL) for post-mission hip bone load capacity, (ii) use of FE hip load capacity to further screen applicants to astronaut corps, (iii) a minimum pre-flight standard for a second long-duration mission, and (iv) a method for assessing which post-mission physical activities might increase an astronaut's risk for fracture after return.

Combined Effects of Simulated Microgravity and Radiation Exposure on Osteoclast Cell Fusion.

The loss of bone mass and alteration in bone physiology during space flight are one of the major health risks for astronauts. Although the lack of weight bearing in microgravity is considered a risk factor for bone loss and possible osteoporosis, organisms living in space are also exposed to cosmic radiation and other environmental stress factors. As such, it is still unclear as to whether and by how much radiation exposure contributes to bone loss during space travel, and whether the effects of microgravity and radiation exposure are additive or synergistic.

Evaluating Bone Loss in ISS Astronauts.

The measurement of bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) is the Medical Assessment Test used at the NASA Johnson Space Center to evaluate whether prolonged exposure to spaceflight increases the risk for premature osteoporosis in International Space Station (ISS) astronauts. The DXA scans of crewmembers' BMD during the first decade of the ISS existence showed precipitous declines in BMD for the hip and spine after the typical 6-mo missions. However, a concern exists that skeletal integrity cannot be sufficiently assessed solely by DXA measurement of BMD.

Bone metabolism and renal stone risk during International Space Station missions.

Bone loss and renal stone risk are longstanding concerns for astronauts. Bone resorption brought on by spaceflight elevates urinary calcium and the risk of renal stone formation. Loss of bone calcium leads to concerns about fracture risk and increased long-term risk of osteoporosis.

Acute exposure to high dose γ-radiation results in transient activation of bone lining cells.

The present studies investigated the cellular mechanisms for the detrimental effects of high dose whole body γ-irradiation on bone. In addition, radioadaptation and bone marrow transplantation were assessed as interventions to mitigate the skeletal complications of irradiation. Increased trabecular thickness and separation and reduced cancellous bone volume fraction, connectivity density, and trabecular number were detected in proximal tibia and lumbar vertebra 14days following γ-irradiation with 6Gy.

Spaceflight-induced bone loss: is there an osteoporosis risk?

Currently, the measurement of areal bone mineral density (aBMD) is used at NASA to evaluate the effects of spaceflight on the skeletal health of astronauts. Notably, there are precipitous declines in aBMD with losses >10 % detected in the hip and spine in some astronauts following a typical 6-month mission in space. How those percentage changes in aBMD relate to fracture risk in the younger-aged astronaut is unknown.

Skeletal health in long-duration astronauts: nature, assessment, and management recommendations from the NASA Bone Summit.

Concern about the risk of bone loss in astronauts as a result of prolonged exposure to microgravity prompted the National Aeronautics and Space Administration to convene a Bone Summit with a panel of experts at the Johnson Space Center to review the medical data and research evidence from astronauts who have had prolonged exposure to spaceflight. Data were reviewed from 35 astronauts who had served on spaceflight missions lasting between 120 and 180 days with attention focused on astronauts who (1) were repeat fliers on long-duration missions, (2) were users of an advanced resistive exercise device (ARED), (3) were scanned by quantitative computed tomography (QCT) at the hip, (4) had hip bone strength estimated by finite element modeling, or (5) had lost >10% of areal bone mineral density (aBMD) at the hip or lumbar spine as measured by dual-energy X-ray absorptiometry (DXA). Because of the limitations of DXA in describing the effects of spaceflight on bone strength, the panel recommended that the U.

Benefits for bone from resistance exercise and nutrition in long-duration spaceflight: Evidence from biochemistry and densitometry.

Exercise has shown little success in mitigating bone loss from long-duration spaceflight. The first crews of the International Space Station (ISS) used the "interim resistive exercise device" (iRED), which allowed loads of up to 297 lb(f) (or 1337 N) but provided little protection of bone or no greater protection than aerobic exercise. In 2008, the Advanced Resistive Exercise Device (ARED), which allowed absolute loads of up to 600 lb(f) (1675 N), was launched to the ISS.

The role of mast cells in parathyroid bone disease.

Chronic hyperparathyroidism (HPT) is a common cause of metabolic bone disease. These studies investigated the underlying cellular and molecular mechanisms responsible for the detrimental actions of elevated parathyroid hormone (PTH) on the skeleton. Bone biopsies from hyperparathyroid patients revealed an association between parathyroid bone disease and increased numbers of bone marrow mast cells.

Quantitative computed tomography reveals the effects of race and sex on bone size and trabecular and cortical bone density.

To examine the effects of race and sex on bone density and geometry at specific sites within the proximal femur and lumbar spine, we used quantitative computed tomography to image 30 Caucasian American (CA) men, 25 African American (AA) men, 30 CA women, and 17 AA women aged 35-45 yr. Volumetric integral bone mineral density (BMD), trabecular BMD (tBMD), and cross sectional area were measured in the femoral neck, trochanter, total femur, and L1/L2 vertebrae. Volumetric cortical BMD (cBMD) was also measured in the femur regions of interest.

Skeletal effects of long-duration head-down bed rest.

Introduction: Skeletal unloading during spaceflight causes regional loss of bone mineral density (BMD), primarily in the spine and lower body regions. This loss of skeletal mass could adversely affect crew health during and after spaceflight and jeopardize mission success. Bed rest has long been used as a spaceflight analog to study the effects of disuse on many body systems, including the skeleton.

Self-assembled monolayer films of phosphonates for bonding RGD to titanium.

Modification of the implant surface with the Arg-Gly-Asp tripeptide (RGD) putatively facilitates osteoblast attachment for improved implant fixation in the laboratory. We compared the histomorphometric and mechanical performance of titanium implants coated with RGD using a novel interface of self-assembled monolayers of phosphonates (RGD/SAMP) and implants coated with RGD using the more conventional thiolate-gold interface (RGD/thiolate-gold). We hypothesized RGD/SAMP-coated implants would show greater bone ongrowth and implant fixation than RGD/thiolate-gold-coated ones.

Effects of parathyroid hormone (1-34) on tibia in an adult rat model for chronic alcohol abuse.

Chronic alcohol abuse is a risk factor for osteoporosis in men. Human recombinant parathyroid hormone (1-34) (PTH) therapy increases bone mass in patients with osteoporosis. The purpose of the present study was to determine whether PTH is effective in increasing bone formation and bone mass in a rat model for established osteopenia caused by chronic alcohol abuse.

Periosteal remodeling at the femoral neck in nonhuman primates.

Unlabelled: Periosteal bone turnover is poorly understood. We documented intramembranous periosteal bone turnover in the femoral neck in intact nonhuman primates and an increase in osteoclast numbers at the periosteal surface in sex steroid-deficient animals. Our studies are the first to systematically document periosteal turnover at the femoral neck.

Hypocalcemia, hypovitaminosis d osteopathy, osteopenia, and secondary hyperparathyroidism 32 years after jejunoileal bypass.

Objective: To detail, for the first time, the results of bone histomorphometry, micro-computed tomography, and the calcium-vitamin D-parathyroid hormone (PTH) axis in a unique patient 32 years after undergoing a jejunoileal bypass (JIB) procedure for obesity.

Methods: A case report is presented, serial results of serum chemistry studies before and after treatment are outlined, and histomorphometric data on a bone biopsy specimen are summarized.

Results: In a 65-year-old woman with chronic lymphedema who had undergone JIB >3 decades earlier, baseline serum studies showed the following: total calcium, 6.

Evidence that the cells responsible for marrow fibrosis in a rat model for hyperparathyroidism are preosteoblasts.

We examined proliferation of cells associated with PTH-induced peritrabecular bone marrow fibrosis in rats as well as the fate of those cells after withdrawal of PTH. Time-course studies established that severe fibrosis was present 7 d after initiation of a continuous sc PTH infusion (40 microg/kg.d).