Lower Serum n-3 Fatty Acid Level in Older Adults with Sarcopenia.

The n-3 fatty acid (FA) has evoked considerable interest as a modifiable factor for maintenance of muscle health owing to its anti-inflammatory properties. To clarify this possibility, we investigated circulating n-3 FA level, a reliable biomarker of FA status in the body, in relation to sarcopenia in a cohort of Asian older adults. Blood samples were collected from 125 participants who underwent comprehensive assessment of muscle mass and function. Serum FA level was measured by gas chromatography/mass spectrometry. Sarcopenia was diagnosed using the cut-off points specified for the Asian population. After adjusting for sex, age, and body mass index, subjects with sarcopenia and those with low muscle strength had 36.5% and 32.4% lower serum n-3 levels (P = 0.040 and 0.030), respectively, than controls. The odds ratios per standard deviation increment in serum n-3 level for sarcopenia and low muscle strength were 0.29 and 0.40 (P = 0.015 and 0.028), respectively. A higher serum n-3 level was significantly associated with greater muscle strength (P = 0.038). These findings suggest a possible protective effect of n-3 FA on human muscle homeostasis. Further well-designed large-scale longitudinal studies are necessary to understand the definite role of circulating n-3 FA level in sarcopenia risk assessment.

Ophthalmoplegia with skin necrosis after a hyaluronic acid filler injection.

Hyaluronic acid filler injection is commonly used for aesthetic purposes. However, many clinicians neglect the possibility of developing vascular occlusion and its devastating sequelae. Besides visual loss after iatrogenic ophthalmic artery occlusion, ophthalmoplegia without blindness is rare but may occur. Here, we report a 23-year-old woman with ptosis, lateral deviation of the right eye, and skin necrosis after hyaluronic acid filler injection. After hyaluronidase injection and steroid pulse therapy, ptosis and eye movement were completely restored. Skin necrosis was treated with a human epithelial growth factor ointment, followed by Nd:YAG laser. Complete healing with minimal scar was achieved.

Intensely Pruritic Papules and Plaques in Waldenstrom's Macroglobulinemia.

Waldenstrom's macroglobulinemia (WM) is lymphoplasmacytoid malignancy that affects B lymphocytes. Cutaneous involvement of WM is rare, but various cutaneous manifestations have been reported. These findings are due to various pathological processes including direct invasion of tumor cells into the skin, deposition of paraproteins, hyperviscosity syndrome, and cryoglobulinemia. A 64-year-old man presented with a 10-day history of pruritic erythematous papules and plaques on his trunk and elbows. The clinical features were suspicious for eczematous dermatitis. However, treatments such as oral antihistamines, topical steroids, ultraviolet light therapy and immunomodulators (dapsone and cyclosporine) were minimally effective. The patient's hemoglobin decreased gradually, and he was referred to the department of hematology. Serum electrophoresis exhibited a monoclonal peak in the ß1 region. The diagnosis of WM was established based on a bone marrow biopsy that revealed 80% lymphoplasma cellularity, staining positive for CD20 and CD79a. However, there was no direct infiltration of tumor cells or immunoglobulin deposition on the skin biopsy. After the patient started rituximab, cyclophosphamide and dexamethasone therapy, anemia and neutropenia gradually improved. His pruritus also markedly subsided. Although there was no evidence of infiltration of WM in the skin lesions, they were thought to be strongly associated with monoclonal gammopathy. This dermatologic feature has not been documented as a nonspecific cutaneous manifestation of WM or monoclonal gammopathy. To clarify the association between intensely pruritic papules/plaques and WM, more reports and further studies could be needed.

Korean Society for Bone and Mineral Research Task Force Report: Perspectives on Intermittent High-dose Vitamin D Supplementation.

An adequate supply of vitamin D is considered necessary for osteoporosis management and fracture prevention. Intermittent high-dose vitamin D supplementation is an effective and convenient way to achieve and maintain sufficient vitamin D status. However, the long-term effectiveness of supplementation for preventing falls and fractures is unclear, and some deleterious effects of such treatments have been reported. Concerning these issues, the Korean Society for Bone and Mineral Research task force team reviewed previous clinical trials and provided the following perspectives based on current evidence: 1) An adequate supply of vitamin D is necessary for preventing falls and fractures in postmenopausal women and men older than 50 years. An oral intake of 800 to 1,000 IU/day of vitamin D is generally recommended. 2) Care should be taken concerning the routine use of intermittent high-dose vitamin D, as large-scale clinical trials showed increased risk of falls or fractures after high-dose vitamin D administration. Intermittent high-dose vitamin D supplementation is recommendable only in cases of malabsorption or when oral administration is not suitable. 3) Monitoring of the serum level of 25-hydroxy-vitamin D (25[OH]D) is advisable, especially when intermittent high-dose vitamin D is used for supplementation. The task force team suggests that a serum 25(OH)D level of >20 ng/mL is generally appropriate for the prevention of osteoporosis, and that a serum 25(OH)D level of >30 ng/mL is probably helpful both for the management of osteoporosis and the prevention of fractures and falls. However, serum 25(OH)D level >50 ng/mL (this value can vary depending on the measurement method used) is unnecessary and may be undesirable. These perspectives are relevant for the management of osteoporosis, falls, or fractures. Other metabolic bone diseases or non-skeletal disorders are not within the scope of these perspectives.

Free Fatty Acid Receptor 4 (GPR120) Stimulates Bone Formation and Suppresses Bone Resorption in the Presence of Elevated n-3 Fatty Acid Levels.

Free fatty acid receptor 4 (FFA4) has been reported to be a receptor for n-3 fatty acids (FAs). Although n-3 FAs are beneficial for bone health, a role of FFA4 in bone metabolism has been rarely investigated. We noted that FFA4 was more abundantly expressed in both mature osteoclasts and osteoblasts than their respective precursors and that it was activated by docosahexaenoic acid. FFA4 knockout (Ffar4(-/-)) and wild-type mice exhibited similar bone masses when fed a normal diet. Because fat-1 transgenic (fat-1(Tg+)) mice endogenously converting n-6 to n-3 FAs contain high n-3 FA levels, we crossed Ffar4(-/-) and fat-1(Tg+) mice over two generations to generate four genotypes of mice littermates: Ffar4(+/+);fat-1(Tg-), Ffar4(+/+);fat-1(Tg+), Ffar4(-/-);fat-1(Tg-), and Ffar4(-/-);fat-1(Tg+). Female and male littermates were included in ovariectomy- and high-fat diet-induced bone loss models, respectively. Female fat-1(Tg+) mice decreased bone loss after ovariectomy both by promoting osteoblastic bone formation and inhibiting osteoclastic bone resorption than their wild-type littermates, only when they had the Ffar4(+/+) background, but not the Ffar4(-/-) background. In a high-fat diet-fed model, male fat-1(Tg+) mice had higher bone mass resulting from stimulated bone formation and reduced bone resorption than their wild-type littermates, only when they had the Ffar4(+/+) background, but not the Ffar4(-/-) background. In vitro studies supported the role of FFA4 as n-3 FA receptor in bone metabolism. In conclusion, FFA4 is a dual-acting factor that increases osteoblastic bone formation and decreases osteoclastic bone resorption, suggesting that it may be an ideal target for modulating metabolic bone diseases.

Higher serum carcinoembryonic antigen levels associate with more frequent development of incident fractures in Korean women: a longitudinal study using the national health insurance claim data.

BACKGROUND: Pro-inflammatory cytokines play important roles in bone metabolism and several studies have shown that carcinoembryonic antigen (CEA) may promote inflammation. We investigated the association of serum CEA levels with the risk of osteoporosis and incident fracture. METHODS: We performed a small cross-sectional study with 302 Korean women and a large, longitudinal study with 7192 Korean women in an average 3-year follow-up period. For the cross-sectional study, bone mineral density (BMD) and bone turnover markers (BTMs) were measured. For the longitudinal study, incident fractures in the follow-up period were identified by using the selected International Classification of Diseases, 10th revision (ICD-10) codes and the nationwide claims database of the Health Insurance Review and Assessment Service of Korea. RESULTS: In the cross-sectional study, serum CEA levels correlated negatively with BMD at the lumbar spine (γ=-0.023; P=0.029) and positively with BTMs (γ=0.122 to 0.138, P=0.002 to P<0.001) after adjustment for confounding variables. In the longitudinal study, 254 (3.5%) women developed incident fractures in the follow-up period (2.8±1.3 years). After adjustment for potential confounders, the hazard ratio (HR) per 1 ng/mL increment of the baseline CEA level for the development of incident fracture was 1.22 [95% confidence interval (CI): 1.05-1.42]. The HR was markedly higher in subjects in the highest CEA quartile category compared with those in the lowest CEA quartile category (HR=1.54, 95% CI: 1.04-2.28). CONCLUSION: Therefore, serum CEA may be a biomarker of the risk of incident fracture in postmenopausal Korean women.

Association between metabolic syndrome and incident fractures in Korean men: a 3-year follow-up observational study using national health insurance claims data.

CONTEXT: Although the prevalence of both metabolic syndrome (MetS) and fractures increases with advancing age, studies on possible associations between these conditions in men are limited and the results are inconsistent. OBJECTIVE: The objective of the study was to clarify the impact of MetS on the male risk of incident fractures. DESIGN AND SETTING: This was a large, longitudinal study with an average 3-year follow-up period. PARTICIPANTS: Korean men (n = 16 078) aged 50 years or older who had undergone comprehensive routine health examinations participated in the study. MAIN OUTCOME MEASURES: Incident fractures found after baseline examinations were identified using selected International Classification of Diseases, tenth revision, codes in the nationwide claims database of the Health Insurance Review and Assessment Service of Korea. RESULTS: In total, 158 men (1.0%) developed incident fractures. The fracture event rates for subjects with and without MetS were 26.2 and 35.7 per 10 000 person-years, respectively. After adjustment for potential confounders, subjects with MetS had a much lower risk of incident fractures than subjects without MetS (hazard ratio 0.662, 95% confidence interval 0.445-0.986). Furthermore, subjects with three and four or more MetS components had a 49.4% and 50.4% lower risk, respectively, of incident fractures compared with the subjects without any MetS components. Importantly, additional adjustment for body mass index eliminated the statistical significance of these associations. CONCLUSION: Our current results indicate that the beneficial effects of MetS in reducing fracture risk could be explained by the general obesity that accompanies MetS, although other related factors, such as greater padding effect, peripheral aromatization, or adipokine changes, may also contribute.