Chronically inadequate sleep results in abnormal bone formation and abnormal bone marrow in rats

Abstract

Insufficient sleep over long durations of the lifespan is believed to adversely affect proper development and healthful aging, although how this might become manifested is unknown. In the present study, rats were repeatedly sleep restricted during 72 days to permit maladaptations to evolve, thereby permitting study. Densitometric and histomorphometric analyses were performed on harvested bone. In sleep-restricted rats, bone lined by osteoid was reduced 45-fold and osteoid thickness was decreased, compared with controls. This corresponded to a decrease in osteoblast number and activity. The percentage of bone lined by osteoclasts did not differ from that of controls. Plasma concentrations of an osteoclast marker (TRACP 5b) were increased in sleep-restricted rats, indicating increased bone resorption. The low amount of new bone formation without a reduction in bone resorption is diagnostic of osteopenia. Bone mineral density was decreased in femurs from sleep-restricted rats compared with control, indicating osteoporosis. Red marrow in sleep-restricted rats contained only 37% of the fat and more than twice the number of megakaryocytes compared to that of the control rats. These findings in marrow suggest changed plasticity and increased hematopoiesis. Plasma concentrations of insulin-like growth factor-1, a known, major mediator of osteoblast differentiation and the proliferation of progenitor cells, was decreased by 30% in sleep-restricted rats. Taken together, these findings suggest that chronically inadequate sleep affects bone metabolism and bone marrow composition in ways that have implications for development, aging, bone healing and repair, and blood cell differentiation.

Obstructive Sleep Apnea and Metabolic Bone Disease: Insights Into the Relationship Between Bone and Sleep

“…Compared to controls, osteoid thickness, osteoblast number/activity, and femoral areal BMD (aBMD) were decreased in sleep-deficient rats, whereas tartrate-resistant acid phosphatase 5b (TRACP5b), a bone resorption marker, was elevated. (90) In general, the effect sizes of sleep disturbance on skeletal measures were small in these studies. However, clinically significant differences may accumulate over time and/or when sleep loss occurs at vulnerable times for bone, such as during bone modeling or gonadal deficiency.…”

“…Rat models also suggest that sleep loss is a risk factor for low bone mass. Compared to controls, osteoid thickness, osteoblast number/activity, and femoral areal BMD (aBMD) were decreased in sleep‐deficient rats, whereas tartrate‐resistant acid phosphatase 5b (TRACP5b), a bone resorption marker, was elevated …”

Osteoporose autorreferida em população idosa: pesquisa de base populacional no município de Campinas, São Paulo

“…Fu et al 34 , in their study on the association between sleep duration and bone mineral density in Chinese women, also proved this association. It is known that an inappropriate sleep affects a healthy aging; however, the specific effects of this kind of sleep regarding bone metabolism are still unknown and limited 34,35 .…”

Influence of sleep deprivation and circadian misalignment on cortisol, inflammatory markers, and cytokine balance

“…Insufficient sleep and circadian misalignment have negative impacts on endocrine, metabolic, cardiovascular, immune, bone, stress, cognition, and neurological health and function (Depner et al, 2014; Dimitrov et al, 2004; Everson et al, 2012; Everson and Szabo, 2011; Haack et al, 2004; Lekander et al, 2013; Markwald et al, 2013; Scheer et al, 2009; Spiegel et al, 1999; Thompson et al, 2014; Weil et al, 2013; Wright et al, 2006; Yu et al, 2013). Sleep deprivation is considered a physiological stressor and a metabolic challenge that is often associated with increased cortisol levels and stress ratings (Chapotot et al, 2001; Dinges et al, 1997; Leproult et al, 1997; Minkel et al, 2012; Parry et al, 2000; Spiegel et al, 1999; von Treuer et al, 1996; Weibel et al, 1995; Weitzman et al, 1983).…”