Moderate COVID-19 Disease Is Associated With Reduced Bone Turnover.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection has been associated with musculoskeletal manifestations, including a negative effect on bone health. Bone formation was found to be reduced in coronavirus disease 2019 (COVID-19) patients. The aim of this case-control study was to determine whether bone metabolism is coupled or uncoupled in COVID-19 patients with moderately severe disease, the latter expressed by the requirement of hospitalization but not intensive care treatment, no need for mechanical ventilation, and a C-reactive protein level of (median [quartiles], 16.0 [4.0; 52.8]) mg/L in serum. Besides standard biochemical markers, serum levels of C-terminal telopeptide of type 1 collagen, tartrate-resistant acid phosphatase, osteocalcin, bone-specific alkaline phosphatase, sclerostin, dickkopf-1, and osteoprotegerin were evaluated in COVID-19-infected patients at the time of hospital admission, along with those of age- and sex-matched noninfected controls. The median age of the 14 female and 11 male infected patients included in the matched-pair analysis was (67 [53; 81]) years. C-terminal telopeptide of type 1 collagen was significantly lower in COVID-19 patients (0.172 [0.097; 0.375] ng/mL) than in controls (0.462 [0.300; 0.649] ng/mL; p = 0.011). The patients' osteocalcin levels (10.50 [6.49; 16.26] ng/mL) were also lower than those of controls (15.33 [11.85, 19.63] ng/mL, p = 0.025). Serum levels of sclerostin and dickkopf-1 were significantly higher in infected patients relative to controls. The remaining parameters did not differ between cases and controls. A limitation of the study was that patients and controls were recruited from different hospitals. Nevertheless, due to the geographical proximity of the two centers, we assume that this fact did not influence the results of the study. Given this limitation, the investigation showed that bone metabolism is altered but remains coupled in patients with moderately severe COVID-19. Therefore, it is important to evaluate bone turnover markers and fracture risk in these patients during the postinfection period. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Severe osteoporosis: Pandemic pick ups

Objective: During COVID-19 pandemic, the access to skeleton investigations for osteoporosis was in many cases postponed, thus consequences on fracture risk (FR) might be expected in terms of not continuing the antiosteoporotic medication or not initiating it if needed. Reduced physical activity might reduce the risk of fall, on one hand, but associated sarcopenia and inhibition of bone formation due to lack of physical exercise increase the FR, on the other hand (1-5). This is a case report of a female with severe osteoporosis who delayed the presentation for diagnostic during first 15 months of pandemic. Case report: This is a 73-year-old female, known with a history of osteoporosis since 2005. She also associates FR: chronic therapy with different SSRIs for depression, multinodular goiter-related hyperthyroidism (which was treated with radioiodine therapy). She has chronic therapy for arteria hypertension, hyperlipemia and hiatal hernia. At diagnostic, after initial lumbar T-score=-3.5 SD, she refused therapy until 2015 (when T-score decreased to -4 SD), thus she began therapy with intravenous ibandronate until 2017 when she experienced a vertebral fracture and daily 20 μg of teriparatide was initiated, starting from a DXA-BMD of 0.783 g/cm2, T-score of 3.1 SD. After 8 months, the treatment was stopped because of her lack of compliance, so she continued with annual zolendronic acid 5 mg until of T-score of -2.6 SD, BMD=0.856 g/cm2. In March 2020, when lockdown pandemic were initiated, she had to come to reassessment, but delayed it, and refused medication based on telemedicine recommendations, except for daily 1000 UI vitamin D. 14 months later, central DXA showed lumbar L1-3 BMD of 0.824 g/cm2, T-score of -2.9 SD, Z-score of -0.7 SD, hip BMD of 0.682 g/cm2, T-score of -2.6 SD, Z-score of -0.4 SD;25-hydroxyvitamin D of 29 ng/mL, PTH of 55 pg/mL, suppressed CrossLaps of 0.287 ng/mL (normal: 0.33-0.782 ng/mL), osteocalcin of 17 ng/mL (normal: 15-46 ng/ mL), P1NP of 27 pg/mL (normal: 15-45 pg/mL);an additional T4 thoracic fracture. Zolendronic acid was further recommended. Conclusion: During pandemic lockdown, the usual serial assays and decision of therapy were less adequate based on telemedicine.

Zolendronic acid after teriparatide: Pandemic observations

Objective: Teriparatide for sever osteoporosis is followed by antiresorptive drugs, and one option in patients with gastric intolerance is zolendronic acid or denosumab (1-5). During pandemic lockdown, the access to bone assessment was limited (1-5). Type 1 diabetic patients are particularly at risk for bone loss, but also for COVID-19 infection, thus the importance of respecting the pandemic rules (1-5). We aim to introduce a female case diagnosed with severe menopausal osteoporosis that was followed during post-teriparatide sequence of medication, including during pandemic days. Case report: This is a type 1 diabetic female of 77 y who was first diagnosed with menopausal osteoporosis 8 y ago (lumbar T-score of-3.1 SD) and started medication with weekly alendronate in addition to vitamin D supplements. After 3 y, she suffered a single spontaneous vertebral fracture thus teriparatide was initiated for 2 y (with good tolerance): lumbar T-score went from -3.1 to -1.9 SD. In the meantime, due to bilateral coxarthrosis she needed bilateral hip replacement. Further on, she continued with biannually denosumab for 8 injections, reaching a lumbar BMD-DXA 0.942 g/cm2, T-score of -2 SD, Z-score of -0.8 SD so an intravenous perfusion with zolendronic acid 5 mg was administered plus vitamin D supplements. While she had no additional fracture and glycated haemoglobin A1c remained around 6.2-6.4%, one year later, the pandemic started, so only bone turnover markers (BTM) were assessed, not DXA: suppressed CrossLaps=0.22 ng/mL (normal: 0.33-0.782 ng/ mL), osteocalcin=11 ng/mL (normal: 15-46 ng/mL), P1NP=27 pg/mL (normal: 15-45 pg/mL). She continued with vitamin D, and 20 months after injection CrossLaps remained low (=22 ng/mL) with normal osteocalcin (=15 ng/mL), P1NP (=28 pg/mL) and stationary BMD. Conclusion: Zolendronic acid effect in osteoporotic patients is easy to access by blood assays if DXA is not available, while lack of BTM increase is suggestive for a good outcome.

Stress Hyperglycemia and Osteocalcin in COVID-19 Critically Ill Patients on Artificial Nutrition.

We aimed to study the possible association of stress hyperglycemia in COVID-19 critically ill patients with prognosis, artificial nutrition, circulating osteocalcin, and other serum markers of inflammation and compare them with non-COVID-19 patients. Fifty-two critical patients at the intensive care unit (ICU), 26 with COVID-19 and 26 non-COVID-19, were included. Glycemic control, delivery of artificial nutrition, serum osteocalcin, total and ICU stays, and mortality were recorded. Patients with COVID-19 had higher ICU stays, were on artificial nutrition for longer (p = 0.004), and needed more frequently insulin infusion therapy (p = 0.022) to control stress hyperglycemia. The need for insulin infusion therapy was associated with higher energy (p = 0.001) and glucose delivered through artificial nutrition (p = 0.040). Those patients with stress hyperglycemia showed higher ICU stays (23 ± 17 vs. 11 ± 13 days, p = 0.007). Serum osteocalcin was a good marker for hyperglycemia, as it inversely correlated with glycemia at admission in the ICU (r = -0.476, p = 0.001) and at days 2 (r = -0.409, p = 0.007) and 3 (r = -0.351, p = 0.049). In conclusion, hyperglycemia in critically ill COVID-19 patients was associated with longer ICU stays. Low circulating osteocalcin was a good marker for stress hyperglycemia.

The Role of Vitamin K in Humans: Implication in Aging and Age-Associated Diseases.

As human life expectancy is rising, the incidence of age-associated diseases will also increase. Scientific evidence has revealed that healthy diets, including good fats, vitamins, minerals, or polyphenolics, could have antioxidant and anti-inflammatory activities, with antiaging effects. Recent studies demonstrated that vitamin K is a vital cofactor in activating several proteins, which act against age-related syndromes. Thus, vitamin K can carboxylate osteocalcin (a protein capable of transporting and fixing calcium in bone), activate matrix Gla protein (an inhibitor of vascular calcification and cardiovascular events) and carboxylate Gas6 protein (involved in brain physiology and a cognitive decline and neurodegenerative disease inhibitor). By improving insulin sensitivity, vitamin K lowers diabetes risk. It also exerts antiproliferative, proapoptotic, autophagic effects and has been associated with a reduced risk of cancer. Recent research shows that protein S, another vitamin K-dependent protein, can prevent the cytokine storm observed in COVID-19 cases. The reduced activation of protein S due to the pneumonia-induced vitamin K depletion was correlated with higher thrombogenicity and possibly fatal outcomes in COVID-19 patients. Our review aimed to present the latest scientific evidence about vitamin K and its role in preventing age-associated diseases and/or improving the effectiveness of medical treatments in mature adults ˃50 years old.