Blood biomarkers of osteoporosis in mild cognitive impairment and Alzheimer’s disease

Abstract

Previous studies revealed some comorbidity of Alzheimer's disease and osteoporosis not only for advanced disease, but also for the incipient conditions cognitive decline and decline of bone mineral density. To detect comorbidity with osteoporosis at a subclinical level, we studied concentrations of biochemical osteoporosis markers in blood plasma of subjects with mild cognitive impairment and mild Alzheimer's disease compared to subjects with primary osteoporosis and age-matched cognitively normal controls in an explorative approach. Regarding disease-spanning molecular pathology we also studied osteoprotegerin, a decoy receptor of RANKL and TRAIL. Equally increased C-terminal collagen fragments, marking bone catabolism, were seen in osteoporosis and Alzheimer's disease (+68%) versus controls. Osteocalcin, marking bone remodelling and anabolism, was concomitantly increased in osteoporosis (+63%), as a trend, and significantly in Alzheimer's disease (+76%). Osteoprotegerin was unchanged between patient groups and controls. 25 (OH) vitamin D plasma levels were low normal and of equal amount in all groups except for the osteoporosis group. These results point to increased bone catabolism and concomitant remodelling/anabolism unrelated to vitamin D state in mild Alzheimer's disease, but not in mild cognitive impairment. This corroborates previous findings of comorbidity of Alzheimer's disease with osteoporosis in the early disease course at the level of biochemical blood markers. Regarding osteoprotegerin, previously reported plasma level increases in Alzheimer's disease were not observed in this study, which does not rule out subtle changes to be detected in larger samples or the possibility that other components of osteoprotegerin pathways are affected in Alzheimer's disease.

APPswe/Aβ regulation of osteoclast activation and RAGE expression in an age-dependent manner

“…2A and 2C). Interestingly, serum OPG protein level is reported to be increased in aged human AD patents, but not early phase of the disease (45,46). Moreover, we also speculate that the reduced BMM cell density in aged mouse bone marrow may cause APPswe-BMMs insensitive to RANKL, another mechanism underlying the decrease of OCs in aged Tg2576 mice.…”

Plasma vitamin d levels and cognitive function in aging women: The nurses' health study

“…Therefore, it is unlikely that reverse causation entirely explains our results. Furthermore, residual confounding by unmeasured or unknown factors [such as depression,(45) low social activity,(46) physical function,(47) fractures,(48) osteoporosis,(49) parathyroid hormone (50), nutritional deficiencies (51, 52)] might have affected vitamin D levels during the 9-year interval. However, residual confounding, although possible, is unlikely to explain all of the results given the stability of the effect estimates from the basic to the fully-adjusted model, which includes multiple health-related factors such as the use of aspirin, history of high blood pressure and of high cholesterol.…”

Progesterone and vitamin D: Improvement after traumatic brain injury in middle-aged rats

“…VDH deficiency has been associated with neurological disorders such as Alzheimer’s disease (Luckhaus et al, 2009), Parkinson’s disease (Evatt et al, 2011); stroke (Kojima et al, 2012; Sun et al, 2012), and some neuropsychiatric diseases (Eyles et al, 2012). It was recently suggested that VDH deficiency can exacerbate injury and its outcome (Balden et al, 2012; Solomon et al, 2011), as well as reduce the beneficial effects of other treatments for TBI (Chatterjee, 2001; McCann et al, 2008; Cekic et al, 2011).…”