Adrian LeBlanc

Cortical and Trabecular Bone Mineral Loss From the Spine and Hip in Long‐Duration Spaceflight

We measured cortical and trabecular bone loss using QCT of the spine and hip in 14 crewmembers making 4‐ to 6‐month flights on the International Space Station. There was no compartment‐specific loss of bone in the spine. Cortical bone mineral loss in the hip occurred primarily by endocortical thinning.

Adaptation of the Proximal Femur to Skeletal Reloading After Long-Duration Spaceflight†

We studied the effect of re‐exposure to Earths gravity on the proximal femoral BMD and structure of astronauts 1 year after missions lasting 4–6 months. We observed that the readaptation of the proximal femur to Earths gravity entailed an increase in bone size and an incomplete recovery of volumetric BMD.

Reduction in proximal femoral strength due to long-duration spaceflight

Loss of bone mass is a well-known medical complication of long-duration spaceflight. However, we do not know how changes in bone density and geometry ultimately combine to affect the strength of the proximal femur as a whole. The goal of this study was to quantify the changes in proximal femoral strength that result from long-duration spaceflight. Pre-and post-flight CT scan-based patient-specific finite element models of the left proximal femur of 13 astronauts who spent 4.3 to 6.5 months on the International Space Station were generated. Loading conditions representing single-limb stance and a fall onto the posterolateral aspect of the greater trochanter were modeled, and proximal femoral strength (F(FE)) was computed. Mean F(FE) decreased from 18.2 times body weight (BW) pre-flight to 15.6 BW post-flight for stance loading and from 3.5 BW pre-flight to 3.1 BW post-flight for fall loading. When normalized for flight duration, F(FE) under stance and fall loading decreased at mean rates of 2.6% (0.6% to 5.0%) per month and 2.0% (0.6% to 3.9%) per month, respectively. These values are notably greater than previously reported reductions in DXA total femoral bone mineral density (0.4 to 1.8% per month). In some subjects, the magnitudes of the reductions in proximal femoral strength were comparable to estimated lifetime losses associated with aging. Although average post-flight proximal femoral strength is greater than forces expected to occur due to falls or normal activities, some subjects have small margins of safety. If proximal femoral strength is not recovered, some crew members may be at increased risk for age-related hip fractures decades after their missions.

Clomiphene protects against osteoporosis in the mature ovariectomized rat

SummaryClomiphene citrate, a mixed estrogen agonist-antagonist, protects mature ovariectomized breeder rats from changes in total body calcium and from deterioration of femur structure. Over 6 months, mature ovariectomized rats took up calcium at the rate of 0.7 ± 0.5 mg/day, while normal controls gained 2.5±0.7 mg/day (mean±SE) as measured by whole body neutron activation analysis. Injections of clomiphene (20 mg/kg/week) kept ovariectomized rats in positive calcium balance at 2.0±0.5 mg/day. Reductions in total femur calcium content, cortical thickness, and visible trabeculae of femurs in ovariectomized animals were prevented by chronic clomiphene administration. These results in animals suggest a possible new line of investigation of the use of antiestrogenic drugs as therapeutic agents for hormone-dependent osteoporosis in animals and humans.

Calf muscle area and strength changes after five weeks of horizontal bed rest

Nine male volunteers participated in a 10 week meta bolic study in which subjects underwent 5 weeks of ambulatory control and 5 weeks of complete horizontal bed rest. Bed rest is a model commonly used to simu late space flight. The changes in muscle area and strength of the calf dorsiflexors and plantar flexors were measured before and after bed rest using magnetic resonance imaging (MRI) and a Cybex II dynamometer. The muscle area of the plantar flexors (gastrocnemius and soleus) decreased 12%, whereas the muscle area of the dorsiflexors was not significantly decreased. The maximal muscle strength of the plantar flexors de creased 26%; the muscle strength of the dorsiflexors was not significantly decreased. These results, which demonstrate differential muscle atrophy and a larger loss in strength relative to muscle area, have important implications in the development of exercise counter measures to be impiemented during space fiight. The results also have implications for patients who have severe orthopaedic disorders and must be bed rested for long periods of time, and for persons who are voluntarily inactive (a large number of the elderly).

Calcium absorption, endogenous excretion, and endocrine changes during and after long-term bed rest.

Negative calcium balance is a known consequence of bed rest, and is manifested in elevated urine and fecal calcium (Ca). Elevated fecal Ca can result from either decreased absorption, increased endogenous fecal excretion, or both. We measured the Ca absorption and endogenous fecal excretion in eight healthy male volunteers before and during 4 months of bed rest. Dual isotope (n = 6) or single isotope (n = 2) methods in conjunction with Ca balance were used to calculate true and net Ca absorption and endogenous fecal excretion. Stool Ca increased from 797 mg/day (mean intake 991 mg/day) to 911 mg/day during bed rest, whereas urine Ca excretion increased from 174 to 241 mg/day. True Ca absorption decreased from 31 +/- 7% of Ca intake pre-bed rest to 24 +/- 2% during bed rest, (p < 0.05) and returned toward pre-bed rest values within 5-6 weeks following reambulation. Endogenous fecal excretion did not change significantly, and therefore, most of the increased fecal Ca resulted from changes in absorption. However, in one individual, endogenous fecal Ca excretion was the major contributor to Ca loss. Ionized Ca and pyridinium crosslinks increased and 1,25(OH)2 vitamin D decreased during bed rest, similar to the decrease in Ca absorption; parathyroid hormone (PTH), calcitonin, serum albumin, phosphorus, and total serum Ca were unchanged. Although alkaline phosphatase, osteocalcin, and PTH were unchanged during bed rest, they were elevated during reambulation. These changes accompanied by increased Ca absorption and balance and decreased ionized and total serum Ca suggest a rebound in bone formation following immobilization.

Future Human Bone Research in Space

Skylab crewmembers demonstrated negative calcium (Ca) balance reaching about -300 mg/day by flight day 84. Limited bone density (BMD) measurements documented that bone was not lost equally from all parts of the skeleton. Subsequent BMD studies during long duration Russian flights documented the regional extent of bone loss. These studies demonstrated mean losses in the spine, femur neck, trochanter, and pelvis of about 1%-1.6% with large differences between individuals as well as between bone sites in a given individual. Limited available data indicate postflight bone recovery occurred in some individuals, but may require several years for complete restoration. Long duration bedrest studies showed a similar pattern of bone loss and calcium balance (-180 mg/day) as spaceflight. During long duration bedrest, resorption markers were elevated, formation markers were unchanged, 1,25 vitamin D (VitD) and calcium absorption were decreased, and serum ionized Ca was increased. Although this information is a good beginning, additional spaceflight research is needed to assess architectural and subregional bone changes, elucidate mechanisms, and develop efficient as well as effective countermeasures. Space research poses a number of unique problems not encountered in ground-based laboratory research. Therefore, researchers contemplating human spaceflight research need to consider a number of unique problems related to spaceflight in their experimental design.

Insulin resistance is associated with decreased clinical status in cystic fibrosis

Patients with cystic fibrosis (CF) frequently have impaired glucose tolerance and progression to diabetes (DM) with clinical features of both insulin-dependent and non-insulin-dependent diabetes. One feature of non-insulin-dependent DM is decreased insulin sensitivity, also known as insulin resistance. The goal of this study was to determine whether patients with CF exhibit insulin resistance and to determine the potential effect of insulin resistance on clinical status. We also sought to determine whether insulin resistance is associated with a specific CF genotype. We studied 18 patients with CF (8 with normal glucose tolerance, 5 with impaired glucose tolerance, 5 with DM), and 20 lean control subjects matched for age, weight, and sex. All control subjects had normal glucose tolerance. The clinical status for each CF patients was determined according to a modified National Institutes of Health scoring system. Each subject underwent a three-step hyperinsulinemic euglycemic clamp (insulin doses of 10, 40, 120 mU/m2 per minute). Results from the 120 mU/m2 per minute infusion defined maximal glucose disposal rate (defined in milligrams per kilogram body weight per minute) at steady state with peripheral insulin levels 195 +/- 20 mU/ml. Subjects with CF demonstrated insulin resistance (control subjects = 13.6 +/- 1.1, patients with CF = 10.2 +/- 1.6 mg/kg per minute; p = 0.003). When each subgroup was compared separately with control subjects, all subgroups were statistically insulin resistant (glucose disposal rate, patients with CF and normal glucose tolerance = 10.8; those with impaired glucose tolerance = 8.4; those with DM = 10.1 mg/kg per minute), and the patients with CF with impaired glucose tolerance were the most insulin resistant. When plotted versus glucose disposal rate, a striking positive correlation between worsened clinical status and insulin resistance (r = 0.85) is demonstrated. Furthermore, there is no correlation between insulin resistance and fasting blood glucose, subject age, or percent ideal body weight (all r values not significant). In conclusion, patients with CF exhibit insulin resistance that is associated with worsened clinical status. We believe it is the combination of insulin resistance and decreased insulin secretion that is responsible for the high incidence of CF-related diabetes.

Changes in intervertebral disc cross-sectional area with bed rest and space flight

Study Design. We measured the cross-sectional area of the intervertebral discs of normal volunteers after an overmight rest; before, during, and after 5 or 17 weeks of bed rest; and before and after 8 days of weightiessness. Objectives. This study sought to determine the degree of expansion of the lumbar discs resulting from bed rest and space flight. Summary of Background Data. Weightlessness and bed rest, an analog for weightlessness, reduce the mechanical loading on the musculoskeletal system. When unioded, intervertebral discs will expand, increasing the nutrtional diffusion distance and altering the mechancial properties of the spine. Methods. Magnetic resonance imaging was used to measure the cross-sectional area and transverse relaxation time (T2) of the intervertebral discs. Results. Overnight or longer bed rest causes expansion of the disc area, which reaches an equilibrium value of about 22% (range 10–40%) above baseline within 4 days. Increases in disc area were associated with modest increases in disc T2. During bed rest, disc height increased approximately 1 mm, about one-half of previous estimates based on body height measurements. After 5 weeks of bed rest, disc area returned to baseline within a few days of ambulation, whereas after 17 weeks, disc area remained above baseline 6 weeks after reambulation. After 8 days of weightlessness, T2, disc area, and lumbar length were not significantly different from baseline values 24 hours after landing. Conclusions. Significant adaptive changes in the intervertebal discs can be expected during weightlessness. These changes, which are rapidly reversible after short duration flights, may be an important factor during and after long-duration missions.

Spinal bone mineral after 5 weeks of bed rest

SummaryPatients put at bedrest for medical reasons lose 1–2% of spinal bone mineral per week. Losses of this magnitude during even shortterm space flights of a few months would pose a serious limitation and require countermeasures. The spinal bone mineral (L2–L4) was determined in 6 healthy males (precision=2%) before and after 5 weeks of complete bed rest. Only one individual had a significant loss (3%) and the −0.9% mean change for the 6, was not significant (P=0.06). The average negative clacium balance during the 5 weeks was 4 g or 0.36% of total body calcium, similar to that reported in other bed-rest studies. Spinal bone loss, however, in healthy bed-rested males is significantly less than reported for bed-rested patients, suggesting that a large loss of spinal bone mineral does not occur during space flight missions lasting 5 weeks or less.