4.Parathormone

*Beyond LEO - Human Health Issues for Deep Space Exploration*

through β-receptors to induce bone mineral loss.

1.Physical factors

static loading [62].

2.Pharmacological factors

3.Bisphosphonates

personal communication).

studies [67].

**5.6 Countermeasures for space-related osteoporosis**

study demonstrated that changes in sympathetic neural traffic to muscles after long-term bedrest of 20 days were significantly correlated with changes in the urinary secretion level of deoxypyridinoline [25, 60], which is used as a specific marker of bone resorption [61]. Based on these findings, exposure to prolonged microgravity may increase sympathetic neural traffic to the bone, which increases the noradrenaline level, thereby inhibiting osteogenesis and facilitating osteolysis

Exercise during weightlessness has been incorporated into the present countermeasure programs; however, exercise alone cannot prevent bone loss. The current exercise program for the ISS is a combination of aerobic and resistive exercise for 2.5 hours, 6 days/week. Data from spaceflight revealed that bone loss occurs mainly in the femur, tibia, calcaneus, and vertebrae. Therefore, exercise should be concentrated on these bones, and impact loading should be primarily provided rather than

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

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

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,

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].

drugs have been proposed to prevent bone loss under microgravity.

**24**

Parathormone has anabolic effects on the bone and also functions in the kidney to stimulate the reabsorption of Ca2+ and increase the synthesis of vitamin D. In this sense, parathormone may stimulate bone formation, increase vitamin D synthesis, and stimulate Ca2+ reabsorption. As suppressing bone reabsorption is favorable for stimulating bone formation during spaceflight, the administration of parathormone is strategically unfavorable.

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 effectiveness of the countermeasure.
