The Human Research Roadmap (HRR) has been published by NASA to systematically target bio-aerospace research to reduce or eliminate risks to health, safety, and performance during and after space exploration. Risks include physiological and performance effects from hazards such as radiation, altered gravity, and hostile environments, as well as unique challenges in medical support, human factors, and behavioral health support. Of the 23 risks identified in this roadmap for humans in space, at least 5 are associated with changes in the function of the musculoskeletal system. The main concerns are about the increase in age-related osteoporosis, the lack of improvement in bone loss after returning from space exploration, and the increased risk of fractures (1).
It is now well established that weightlessness during space exploration causes osteoporosis. Loss of bone mass throughout the body and in the legs, which are rich in cortical bone, is 0.3–0.4% per month. The reduction in bone mass in the trabecular part of the bone seems to be greater than in the cortical part (2, 3).
Histomorphometric studies of rats that experienced space exploration for different periods showed changes in bone cortex and sponge, a transient increase in bone resorption, and a permanent decrease in bone production (4, 5).
Data on interventions to maintain stable bone metabolism and prevent bone loss during space exploration are limited. Ingesting high amounts of calcium and vitamin D supplements during space exploration did not prevent osteoporosis. The additives did not prevent an increase in bone resorption although they did prevent an increase in serum calcium levels (6, 7).
Zinc is an essential element that has many physiological roles in biochemical processes, especially growth in humans and animals. Several zinc-dependent hormones and enzymes are involved in bone metabolism. Zinc stimulates cell differentiation, cell proliferation, and mineralization in osteoblasts and thus stimulates bone production. From a molecular point of view, zinc stimulates gene expression in various proteins including Runx2/Cbfa 1 (transcription factor for osteoblast cell differentiation), type I collagen, alkaline phosphatase, and osteocalcin in cells (8). The concentration of osteocalcin, which is secreted from osteoblastic cells in the culture medium, rises significantly after the addition of zinc. Adding zinc to culture stimulates the production of bone growth factors and bone matrix proteins that are involved in promoting bone formation and mineralization. DNA polymerase enzyme involved in DNA production is a zinc-dependent enzyme. Zinc may cause DNA production by activating the DNA polymerase enzyme in bone tissue osteoblasts (9).
Bone biomarkers are used for research as well as to monitor the therapeutic effect of elements on bone turnover. Biomarkers of bone formation are products that active osteoblasts express at different stages of their maturation or bone enzymes. Biomarkers that are widely measured in serum or plasma include bone-specific alkaline phosphatase (BSAP), and osteocalcin, which were measured in the present study (10).
Bone-specific alkaline phosphatase is a biomarker involved in bone formation. Alkaline phosphatase (ALP, ALKP, ALPase, Alk Phos) (EC18.104.22.168) is a hydrolase enzyme (associated with cell membranes) that is responsible for removing phosphate groups from many types of molecules, including nucleotides, proteins, and alkaloids. Alkaline phosphatase is produced by osteoblasts (11).
Osteocalcin is a non-collagenous protein made by osteoblasts. Osteocalcin is found in bone and has a metabolic role, and is prosteoblastic. Osteocalcin is involved in bone mineralization and calcium homeostasis. Serum osteocalcin levels are determined by bone formation and the number of osteoblasts. Serum osteocalcin levels are determined by histomorphometry and calcium analysis and are introduced as a biomarker of bone formation. Osteocalcin is one of a few proteins that are specific to the skeletal system (12). Osteocalcin and alkaline phosphatase are good biomarkers for the study of osteoblast activity. On the other hand, zinc is essential for osteoblast activity, collagen synthesis, and alkaline phosphatase activity (13).
Considering that the changes in bone during space exploration in astronauts are one of the most important issues in astronomy, this study was designed to determine the changes in bone biomarkers with and without zinc sulfate in an experimental model of space exploration.
Due to the high cost of space exploration, efforts have been made to artificially create weightlessness on Earth. One of these methods, hanging a rat by its tail, is widely used as a laboratory model of space exploration. This technique simulates the effects of weightlessness on the bones and muscles of the animal's hind legs. It also allows the blood flow to be simulated, like a human being in a state of weightlessness, in which the blood flow tends to shift towards the animal's head and chest (14).