2.Pharmacological factors

As bone mass is sufficient at the onset of the spaceflight, the optimal strategy for the pharmacotherapy against bone loss is the prevention of bone loss, not the acceleration of bone formation, when loading is removed during spaceflight. Several drugs have been proposed to prevent bone loss under microgravity.

### 3.Bisphosphonates

Bisphosphonates have two phosphonate (PO3) groups and are similar in structure to pyrophosphate. They bind to hydroxyapatite in bone matrix and prevent bone loss by inhibiting osteoclastic bone resorption. Bisphosphonates have been demonstrated to be effective in preventing bone loss during bedrest studies [63–66]. Among several types of bisphosphonates, pamidronate has been confirmed to suppress bone mineral loss and to prevent the formation of renal stones during bedrest studies [67].

In 2010, LeBlanc and Matsumoto [68] proposed an experiment for the effectiveness of bisphosphonate as a countermeasure to spaceflight-induced bone loss. The astronauts chose either oral administration of alendronate at 70 mg once per week or intravenous administration of zoledronate at 4 mg before the flight, and their bone densities were examined by DXA, QCT, and pQCT, and bone metabolism markers, including bone formation and resorption markers, and renal stone formation were assessed. One of the co-investigators (Ohshima) reported successful suppression of spaceflight-induced bone loss and renal stone formation (Ohshima, personal communication).

The disadvantages of bisphosphonates are local irritation of the upper gastrointestinal (GI) tract and poor absorption from the GI tract. Therefore, the oral administration of bisphosphonates requires drinking 200 mL of water while remaining in an upright posture for at least 30 min until after their first meal of the day to facilitate delivery to the stomach. This poses a problem as there is no upright posture in space due to microgravity. Another potential problem is osteonecrosis of the maxilla and the mandible, although the incidence is low [69]. These osteonecrotic or osteolytic phenomena always accompany physiological stress (mastication), iatrogenic trauma (tooth extraction/denture injury), or tooth infection [70, 71].

**25**

unchanged.

*Effects of Microgravity on Human Physiology DOI: http://dx.doi.org/10.5772/intechopen.90700*

to stimulate the reabsorption of Ca2+

parathormone is strategically unfavorable.

the effectiveness of the countermeasure.

**6. Immunology and hematology**

**6.1 Space anemia**

after more than 3 months.

synthesis, and stimulate Ca2+

4.Parathormone

Bisphosphonates are difficult to metabolize, and high concentrations of them are maintained in the bones for long periods. As bone formation is closely coupled with bone turnover, long-term use of the compound with resultant suppression of bone turnover can compromise healing of even physiological microinjuries within the bone. Osteonecrosis of the maxilla and mandible likely results from the inability of the hypodynamic and hypovascular bone to meet the increased demand for repair and remodeling because several alterations are associated with this necrosis.

Parathormone has anabolic effects on the bone and also functions in the kidney

favorable for stimulating bone formation during spaceflight, the administration of

In conclusion, it is favorable to administer bisphosphonate orally under artificial gravity with exercise in order to prevent osteoporosis in space. Monitoring the blood and urine samples on the ISS or spacecraft by a simple method is necessary to assess

The circulatory blood volume is 5 L on average and contains plasma and cellular components, including erythrocytes, leukocytes (neutrophils, eosinophils, basophils, and lymphocytes), and platelets [72–74]. Among them, reduction in cellular components, especially erythrocytes (RBC), is associated with anemia, whereas the

In the early stages of space development, cases of "space anemia" (hematocrit reduction) were reported on Gemini, Apollo, Skylab, and Shuttle missions and in the cosmonauts in the Salyut and Mir missions. However, in spaceflight, microgravity causes cephalad fluid shift, meaning this "space anemia" was actually a misinterpretation of symptoms. The true effects of microgravity can be measured through the total RBC count calculated from the hematocrit and plasma volume measurements. In this way, "space anemia" corresponded to a reduction in the total RBC count. After 10 days aboard Spacelab-1, the total RBC count was reduced by 9% and by 15% after several weeks. After returning to Earth, the total RBC count did not recover even after 6 weeks and, in the case of Skylab astronauts, had not recovered

This suggested that microgravity is responsible for "space anemia," and many investigations were carried out to reveal whether anemia is the result of an increase in RBC destruction or a decrease in their production. Using labeled RBC by the uptake of 14C glycine, RBC destruction was found to be three times greater in rats having flown aboard Cosmos-782 than in the control rats. On the other hand, reduced RBC production is unlikely because the number of stem cells measured by the number of cellular colonies that developed in vitro from samples of bone marrow taken from rats that flew aboard the Soviet Biosatellite—2044 for 14 days—was

Human studies carried out by [75] on Shuttle missions for 9 to 14 days demonstrated that space anemia is due mainly to a lower production of RBC, causing

function of leukocytes is related to immunological response.

this sense, parathormone may stimulate bone formation, increase vitamin D

and increase the synthesis of vitamin D. In

reabsorption. As suppressing bone reabsorption is

### *Effects of Microgravity on Human Physiology DOI: http://dx.doi.org/10.5772/intechopen.90700*

Bisphosphonates are difficult to metabolize, and high concentrations of them are maintained in the bones for long periods. As bone formation is closely coupled with bone turnover, long-term use of the compound with resultant suppression of bone turnover can compromise healing of even physiological microinjuries within the bone. Osteonecrosis of the maxilla and mandible likely results from the inability of the hypodynamic and hypovascular bone to meet the increased demand for repair and remodeling because several alterations are associated with this necrosis.
