Vitamin D: 100 years of discoveries, yet controversy continues.

Over the past 100 years, many major breakthroughs and discoveries have occurred in relation to vitamin D research. These developments include the cure of rickets in 1919, the discovery of vitamin D compounds, advances in vitamin D molecular biology, and improvements in our understanding of endocrine control of vitamin D metabolism. Furthermore, recommended daily allowances for vitamin D have been established and large clinical trials of vitamin D, aimed at clarifying the effect of Vitamin D in the prevention of multiple diseases, have been completed. However, disappointingly, these clinical trials have not fulfilled the expectations many had 10 years ago. In almost every trial, various doses and routes of administration did not show efficacy of vitamin D in preventing fractures, falls, cancer, cardiovascular diseases, type 2 diabetes, asthma, and respiratory infections. Although concerns about side-effects of long-term high-dose treatments, such as hypercalcaemia and nephrocalcinosis, have been around for four decades, some trials from the past 5 years have had new and unexpected adverse events. These adverse events include increased fractures, falls, and hospitalisations in older people (aged >65 years). Several of these clinical trials were powered appropriately for a primary outcome but did not include dose response studies and were underpowered for secondary analyses. Furthermore, more attention should be paid to the safety of high doses of vitamin D supplementation, particularly in older people. In addition, despite universal recommendations by osteoporosis societies for combining calcium supplements with vitamin D there remains insufficient data about their efficacy and effect on fracture risk in the highest risk groups. More trials are needed for people with severe vitamin D deficiency (ie, serum 25-hydroxyvitamin D <25nmol/L [10ng/mL]). In this Personal View, we summarise and discuss some of the major discoveries and controversies in the field of vitamin D.

Secondary fracture rates and risk factors 1 year after a proximal femoral fracture under FLS.

INTRODUCTION: We aimed to investigate the secondary fracture rates and risk factors in patients with proximal femoral fractures using fracture liaison service (FLS) during the coronavirus disease (COVID)-19 pandemic. MATERIALS AND METHODS: In this multi-center prospective cohort study, patients with proximal femoral fractures who were treated surgically at three hospitals from April 2020 to March 2021 were included. Follow-up examinations at 6 and 12 months postoperatively were conducted to investigate the clinical data and ascertain whether osteoporosis treatment could be continued. RESULTS: A total of 316 patients with proximal femoral fractures were registered. During the follow-up period, 17 patients died and 67 patients could not visit the hospitals owing to the COVID-19 pandemic. In total, 172 patients who could be followed-up 12 months postoperatively were examined using dual-energy X-ray absorptiometry during hospitalization; underwent postoperative osteoporosis treatment, mainly with bisphosphonates (89.5%); and were administered medications continuously. Secondary fractures occurred within 1 year in 14 patients (8.1%). Multivariate analysis showed that patients who used sleeping pills and had a lower functional independence measure had an increased risk for developing secondary fractures. CONCLUSION: During the COVID-19 pandemic, secondary fractures can be prevented if the patients can be followed and osteoporosis treatment can be continued. Conversely, despite adequate osteoporosis drug examination and treatment, a certain number of secondary fractures still occurred. The finding that postoperative osteoporosis therapy using routine medications and rehabilitation is associated with secondary fractures may support the importance of establishing clinical standards consisting of a multidisciplinary collaboration for FLS.

Vitamin D Status Is Negatively Related to Insulin Resistance and Bone Turnover in Chinese Non-Osteoporosis Patients With Type 2 Diabetes: A Retrospective Cross-Section Research.

BACKGROUND AND OBJECTIVES: Vitamin D status is closely related to blood glucose and bone metabolism in patients with type 2 diabetes (T2DM). Vitamin D affects bone density and bone metabolism, leading to osteopenia and osteoporosis. Insulin resistance increases the risk of osteoporosis in patients with T2DM. Our previous studies have shown a negative correlation between insulin resistance and 25-hydroxy vitamin D [25(OH)D] levels. The aim of the present study was to determine the association between vitamin D status and insulin resistance and bone metabolism in patients with T2DM. SUBJECTS AND METHODS: A retrospective cross-section research was carried out among 109 non-osteoporosis patients with T2DM. Their fasting blood glucose (FBG), 25(OH)D, fasting blood insulin (FINS), glycosylated hemoglobin (HbA1c), serum creatinine (SCr), calcium (Ca), phosphorus (P), insulin-like growth factor-1 (IGF-1), bone alkaline phosphatase (BALP), body mass index (BMI), glomerular filtration rate (eGFR), homeostatic model estimates of insulin resistance (HOMA-IR), and calcium-phosphorus product were measured routinely. RESULTS: Both in men and women, 25(OH)D was negatively correlated with BALP (ß = -0. 369, p ≤ 0.001)and HOMA-IR (ß = -0.349, p ≤ 0.001), and positively associated with IGF-1(ß = 0.672, p ≤ 0.05). There was a negative correlation between HOMA-IR and IGF-1 (ß = -0.464, p ≤ 0.001), and a positive correlation between HOMA-IR and BALP (ß = 0.344, p ≤ 0.05), adjusted by confounding factors. CONCLUSION: Our study demonstrates that 25(OH)D concentrations are negatively correlated with insulin resistance and bone turnover. Insulin resistance increases with the decrease of 25(OH)D concentration, which can enhance bone turnover, and increases the risk of osteoporosis in non-osteoporosis patients with T2DM. This is the first study to clarify the relationship between serum vitamin D status, insulin resistance, and bone metabolism in non-osteoporosis patients with T2DM in China.

Concurrent Treatment with Vitamin K2 and D3 on Spine Fusion in Patients with Osteoporosis-Associated Lumbar Degenerative Disorders.

STUDY DESIGN: A prospective and nonrandomized concurrent controlled trial. OBJECTIVE: To address the early effects of concurrent treatment with vitamin K2 and vitamin D3 on fusion rates in patients who have undergone spinal surgery. SUMMARY OF BACKGROUND DATA: Intervertebral pseudarthrosis has been reported after transforaminal lumbar interbody fusion (TLIF) or posterior lumbar interbody fusion (PLIF), especially in patients with osteopenia or osteoporosis. No study has assessed the early effects of concurrent treatment with vitamin K2 and vitamin D3 on fusion rates. METHODS: Patients with osteopenia or osteoporosis who underwent TLIF or PLIF in our department were included. Patients in the VK2+VD3 group received vitamin K2, vitamin D3, and calcium treatment, whereas subjects in the control group only received calcium and vitamin D3. Spine fusion was evaluated by computed tomography. The Japanese Orthopedic Association Back Pain Evaluation Questionnaire (JOA-BPEQ) and visual analog scale (VAS) were used to assess the clinical and neurological symptoms. Bone mineral density (BMD) and bone metabolism markers were measured for osteoporotic evaluation. RESULTS: Seventy-eight patients were included, and nine patients subsequently discontinued because of 2019-nCoV. At six months postoperatively, complete fusion rates were significantly higher in the VK2+VD3 group than that in the control group (91.18% vs 71.43%, P = 0.036). At six months postoperatively, BMD was increased in the VK2+VD3 group and was higher than that in the control group, although there was no significant difference. At three months postoperatively, a significant increase in procollagen type I amino terminal propeptide (91.81%) and a slight decrease in C-terminal end peptide (8.06%) were observed in the VK2+VD3 group. In both groups, the JOA-BPEQ and VAS scores were significantly improved after spine surgery. CONCLUSION: Administration of vitamin K2 and vitamin D3 can increase lumbar interbody fusion rates, improve clinical symptoms, promote bone information, and avoid further decline in BMD within six months after TLIF or PLIF.Level of Evidence: 3.

Osteosarcopenia, the co-existence of osteoporosis and sarcopenia, is associated with social frailty in older adults.

BACKGROUND: Osteosarcopenia is a newly described, aging-associated condition. Social frailty is an important condition whose prevalence may have risen by physical distancing during the coronavirus disease 2019 pandemic. However, the relationship between these two remains unclear. AIMS: To examine the association between osteosarcopenia and social frailty. METHODS: This cross-sectional study was conducted using data from outpatients visiting general geriatric hospital frailty clinics. Bone mineral density (BMD) and muscle mass were measured using dual X-ray absorptiometry. Osteoporosis was defined as a BMD of < 70% of the young adult mean, according to the Japan Osteoporosis Society. Sarcopenia was diagnosed as per the Asian Working Group for Sarcopenia 2019 recommendation. Osteosarcopenia was defined as the co-existence of osteoporosis and sarcopenia. We defined social frailty using a questionnaire comprising four items: general resources, social resources, social behavior, and basic social needs. Ordinal logistic regression analysis was performed with social frailty status and osteosarcopenia as the dependent and independent variables, respectively. RESULTS: We included 495 patients (mean age = 76.5 ± 7.2 years) in the analysis; of these, 58.2% were robust and 17.2%, 13.5%, and 11.1% had osteoporosis alone, sarcopenia alone, and osteosarcopenia, respectively. Social frailty prevalence increased stepwise from 8.0% in robust patients to 11.8%, 17.9%, and 29.1% among those with osteoporosis alone, sarcopenia alone, and osteosarcopenia, respectively (P < 0.001). Logistic regression analysis revealed that only osteosarcopenia was significantly associated with social frailty (pooled odds ratio: 2.117; 95% confidence interval: 1.104-4.213). DISCUSSION: Comprehensive assessment of osteosarcopenia and social frailty is needed for disability prevention in older adults.

Metabolic syndrome in the era of COVID-19 outbreak: impact of lockdown on cardiometabolic health.

PURPOSE: COVID-19 pandemics and cardiometabolic health are mutually interconnected. Chronic metabolic diseases are known risk factors for increased mortality after SARS-CoV-2 infection. In turn, COVID pandemics imposed sudden changes in lifestyle and social isolation with consequent potential cardiometabolic sequelae. The present study aimed at investigating the impact of changes in lifestyle and social life on metabolic profile in hyperprolactinemic or osteoporotic patients without pre-existing cardiometabolic diseases at the time of COVID-19. METHODS: The primary study outcome measurement was the prevalence of obesity, arterial hypertension, impaired glucose tolerance (IGT) or diabetes mellitus (DM), dyslipidemia and metabolic syndrome after COVID-19 outbreak. Seventy-four patients (21 men and 53 women, aged 51.8 ± 17.8 years) were admitted to the outpatient clinic of the Neuroendocrine Disease Unit at University "Federico II" of Naples, Italy, as per their routine clinical practice because of tumoral and non-tumoral hyperprolactinemia in 52 patients (70.3%), and osteoporosis/osteopenia in 22 (29.7%). Among female patients, 25 (47.2%) were at menopausal age. RESULTS: At the end of lockdown, prevalence of obesity (from 37.8% to 51.3%, p < 0.0001), dyslipidemia (from 28.4 to 48.6%, p = 0.003) and metabolic syndrome (from 14.9 to 27%, p < 0.0001) significantly increased compared to pre-COVID evaluation. No significant change was found in the prevalence of arterial hypertension and IGT/DM. CONCLUSION: SARS-CoV-2 outbreak has led to a rapid increase in the prevalence of metabolic syndrome, potentially contributing to the increased COVID-19 related mortality.

Epidemiologic characteristics of traumatic fractures during the outbreak of coronavirus disease 2019 (COVID-19) in China: A retrospective & comparative multi-center study.

PURPOSE: Amid the outbreak of coronavirus disease 2019 (COVID-19), effective measures have been taken in China to suggest people wearing masks and staying at home. The majority of the people stayed at home, which had an obvious impact on the occurrence of traumatic fractures. This study aimed to describe the epidemiologic characteristics of traumatic fractures during the COVID-19, and provide reference for targeted control measures for the whole world by proposing China's experiences. METHODS: This was a retrospective & comparative multi-center study with data obtained from 11 hospitals in five provinces of China. Patients were enrolled into this study, who sustained fractures from 20 January to 19 February 2020 and the same period in 2019 (based on Chinese lunar calendar). All patients were divided into two groups: epidemic group (admitted in 2020) and control group (admitted in 2019). The data of patients' demographics (age and gender), injury related data (fracture type, fractured site, osteoporosis fracture, concurrent fractures, injury mechanism, places where fracture occurred, ISS score, Gustilo-Anderson Classification for open fracture), mortality and treatment modality were compared between the two groups. RESULTS: A total of 2,489 patients with 2,590 fractures were included. In the epidemic group, there were 865 patients, including 483 (55.8%) males and 382 (44.2%) females with an average age of 53.1 ± 23.1 years (range, 1 to 105). In the control group, there were 1,624 patients, including 876 (53.9%) males and 748 (46.1%) females with an average age of 51.2 ± 21.5 years (range, 1 to 98). Patients in the epidemic group was significantly older than those in the control group (t=-2.046, P = 0.045). For epidemic group, the mostly commonly involved age group was elderly patients, whereas it was middle-aged adults for the control group (χ2 = 14.642, P = 0.002). For epidemic group, a total of 576 (66.6%) patients had their fracture occurring at home, while in the control group there was 183 (11.3%). The proportion rates of low energy injuries (79.1%, 684/865), osteoporotic fractures (32.5%, 294/906) and closed fractures (94.5%, 817/865) in the epidemic group were significantly higher when compared to the control group, respectively (34.4%, 559/1624; 26.9%, 453/1684; 91.9%, 1,493/1692; all P<0.05). The proportion rates of Gustilo-Anderson classification (5.5%, 16/865), concurrent fractures (2.3%, 20/865), and injury severity score (15.6 ± 6.7) in epidemic group were significantly lower than those in the control group, respectively (52.8%, 199/1624; 3.9%, 63/1624; 20.1 ± 8.7; all P<0.05). No positive case with COVID-19 was diagnosed in the epidemic group. The mortality rate in the epidemic group (0.46%) was similar with that in the control group (0.43%). CONCLUSIONS: Our findings confirmed the importance of the measures to restrict people's movement and wear masks in the prevention of the spread of COVID-19. The epidemiological characteristics of traumatic fractures amid the epidemic changes dramatically, and more attempts should be focused on the prevention of low energy injuries of elderly population.

Standardized out-patient diagnosis and treatment process for osteoporosis clinics during the COVID-19 pandemic.

Since the end of 2019, China and other regions around the world have been facing a pandemic of novel coronavirus pneumonia (COVID-19). The virus is highly transmissible, and the human population is generally susceptible. Most patients with osteoporosis are postmenopausal women or elderly people with hypoimmunity, so the osteoporosis clinic has become a new hotspot for corona virus infection. During the COVID-19 pandemic, it is necessary to establish standardized out-patient protocols to provide safe and effective treatment for osteoporosis patients and medical staff. In an osteoporosis clinic, we advocate the following suggestions to prevent and control osteoporosis during the pandemic period: (1) specialized diagnosis and treatment techniques for osteoporosis patients in the outpatient care, including enhancing the prevention for outpatient medical staff, strengthening awareness of COVID-19 prevention, strictly screening outpatients with COVID-19 infection, and insistent administration of anti-osteoporosis drugs during outbreaks; (2) home prevention for osteoporosis patients including keeping windows open, exposing them to sunlight, supplementing them with enough protein, exercising regularly, and administrating calcium supplements; and (3) simplifying the follow-up and evaluation of osteoporosis using online platforms.