Consensus Statement on Vitamin D Status Assessment and Supplementation: Whys, Whens, and Hows.

The 6th International Conference, "Controversies in Vitamin D," was convened to discuss controversial topics, such as vitamin D metabolism, assessment, actions, and supplementation. Novel insights into vitamin D mechanisms of action suggest links with conditions that do not depend only on reduced solar exposure or diet intake and that can be detected with distinctive noncanonical vitamin D metabolites. Optimal 25-hydroxyvitamin D (25(OH)D) levels remain debated. Varying recommendations from different societies arise from evaluating different clinical or public health approaches. The lack of assay standardization also poses challenges in interpreting data from available studies, hindering rational data pooling and meta-analyses. Beyond the well-known skeletal features, interest in vitamin D's extraskeletal effects has led to clinical trials on cancer, cardiovascular risk, respiratory effects, autoimmune diseases, diabetes, and mortality. The initial negative results are likely due to enrollment of vitamin D-replete individuals. Subsequent post hoc analyses have suggested, nevertheless, potential benefits in reducing cancer incidence, autoimmune diseases, cardiovascular events, and diabetes. Oral administration of vitamin D is the preferred route. Parenteral administration is reserved for specific clinical situations. Cholecalciferol is favored due to safety and minimal monitoring requirements. Calcifediol may be used in certain conditions, while calcitriol should be limited to specific disorders in which the active metabolite is not readily produced in vivo. Further studies are needed to investigate vitamin D effects in relation to the different recommended 25(OH)D levels and the efficacy of the different supplementary formulations in achieving biochemical and clinical outcomes within the multifaced skeletal and extraskeletal potential effects of vitamin D.

Vitamin D status and supplementation before and after Bariatric Surgery: Recommendations based on a systematic review and meta-analysis.

Bariatric surgery is associated with a postoperative reduction of 25(OH) vitamin D levels (25(OH)D) and with skeletal complications. Currently, guidelines for 25(OH)D assessment and vitamin D supplementation in bariatric patients, pre- and post-surgery, are still lacking. The aim of this work is to analyse systematically the published experience on 25(OH)D status and vitamin D supplementation, pre- and post-surgery, and to propose, on this basis, recommendations for management. Preoperatively, 18 studies including 2,869 patients were evaluated. Prevalence of vitamin D insufficiency as defined by 25(OH)D < 30 ng/mL (75 nmol/L) was 85%, whereas when defined by 25(OH)D < 20 ng/mL (50 nmol/L) was 57%. The median preoperative 25(OH)D level was 19.75 ng/mL. After surgery, 39 studies including 5,296 patients were analysed and among those undergoing either malabsorptive or restrictive procedures, a lower rate of vitamin D insufficiency and higher 25(OH)D levels postoperatively were observed in patients treated with high-dose oral vitamin D supplementation, defined as ≥ 2,000 IU/daily (mostly D3-formulation), compared with low-doses (< 2,000 IU/daily). Our recommendations based on this systematic review and meta-analysis should help clinical practice in the assessment and management of vitamin D status before and after bariatric surgery. Assessment of vitamin D should be performed pre- and postoperatively in all patients undergoing bariatric surgery. Regardless of the type of procedure, high-dose supplementation is recommended in patients after bariatric surgery.

Assessment of DXA derived bone quality indexes and bone geometry parameters in early breast cancer patients: A single center cross-sectional study.

Background: Bone mineral density (BMD) lacks sensitivity in individual fracture risk assessment in early breast cancer (EBC) patients treated with aromatase inhibitors (AIs). New dual-energy X-ray absorptiometry (DXA) based risk factors are needed. Methods: Trabecular bone score (TBS), bone strain index (BSI) and DXA parameters of bone geometry were evaluated in postmenopausal women diagnosed with EBC. The aim was to explore their association with morphometric vertebral fractures (VFs). Subjects were categorized in 3 groups in order to evaluate the impact of AIs and denosumab on bone geometry: AI-naive, AI-treated minus (AIDen-) or plus (AIDen+) denosumab. Results: A total of 610 EBC patients entered the study: 305 were AI-naive, 187 AIDen-, and 118 AIDen+. In the AI-naive group, the presence of VFs was associated with lower total hip BMD and T-score and higher femoral BSI. As regards as bone geometry parameters, AI-naive fractured patients reported a significant increase in femoral narrow neck (NN) endocortical width, femoral NN subperiosteal width, intertrochanteric buckling ratio (BR), intertrochanteric endocortical width, femoral shaft (FS) BR and endocortical width, as compared to non-fractured patients. Intertrochanteric BR and intertrochanteric cortical thickness significantly increased in the presence of VFs in AIDen- patients, not in AIDen+ ones. An increase in cross-sectional area and cross-sectional moment of inertia, both intertrochanteric and at FS, significantly correlated with VFs only in AIDen+. No association with VFs was found for either lumbar BSI or TBS in all groups. Conclusions: Bone geometry parameters are variably associated with VFs in EBC patients, either AI-naive or AI treated in combination with denosumab. These data suggest a tailored choice of fracture risk parameters in the 3 subgroups of EBC patients.

A case of aggressive systemic mastocytosis with bulky lymphadenopathy showing response to midostaurin.

Management of systemic mastocytosis is an emerging challenge which requires a multidisciplinary diagnostic approach and personalized treatment strategy. Midostaurin can rapidly reduce the disease burden, also in cladribine refractory cases.

Usefulness of Dual X-ray Absorptiometry-Derived Bone Geometry and Structural Indexes in Mastocytosis.

Reduced bone mass with or without fragility fractures is a common feature of mastocytosis, particularly in adult males. However, bone mineral density does not account for all the fragility fractures, being a part of them attributable to impairment in bone quality. Aim of this study is to assess the usefulness of DXA-derived geometry and structural indexes in the assessment of bone status in mastocytosis. Ninety-six consecutive patients (46 women and 50 men) affected by cutaneous (CM) or systemic (SM) mastocytosis were studied. Mean age (± SD) was 53.3 ± 14.23. Spine lateral X-rays for Genant's scale, DXA for lumbar (L) and femoral (F) bone mineral density (BMD), bone strain index (BSI), lumbar trabecular bone score (TBS), and hip structural analysis (HSA) were performed. Among the laboratory variables, data of serum tryptase were reported. Tryptase was higher in SM (p = 0.035), inversely correlated with LBMD (r = - 0.232; p = 0.022) and TBS (r = - 0.280; p = 0.005), and directly with L-BSI (r = 0.276; p = 0.006). L-BSI remained statistically significant (p = 0.006; adjusted R2 = 0.101) together with mastocytosis (SM or CM: p = 0.034) in the multivariate regression model with tryptase as dependent variable, being LBMD and TBS not statistically significant (p = 0.887, and p = 0.245, respectively). Tryptase increased about 22 units for each unit increase of L-BSI and about 18 units for SM against CM. L-BSI was lower (p = 0.012), while FN-BSI and FT-BSI were higher in women (p < 0.001) than in men. HSA indexes were significantly higher in men, particularly with SM. SM is a risk factor for reduced bone mass, texture and strength. Since mean L-BSI and Z-modulus of all the femoral sites are statistically higher in men than in female, it could be argued that men have a better femoral bone resistance to bending forces than women, but a worse lumbar bone resistance to compressive loads. DXA indexes of bone quality are useful in mastocytosis' bone assessment and its clinical management.

Body composition with dual energy X-ray absorptiometry: from basics to new tools.

Dual-energy X-ray absorptiometry (DXA) in nowadays considered one of the most versatile imaging techniques for the evaluation of metabolic bone disorders such as osteoporosis, sarcopenia and obesity. The advantages of DXA over other imaging techniques are the very low radiation dose, its accuracy and simplicity of use. In addition, fat mass (FM) and lean mass (LM) values by DXA shows very good accuracy compared to that of computed tomography and magnetic resonance imaging. In this review we will explain the technical working principles of body composition with DXA, together with the possible limitations and pitfalls that should be avoided in daily routine to produce high-quality DXA examinations. We will also cover the current clinical practical application of whole body DXA values, with particular emphasis on the use of LM indices in the diagnostic workup of reduced muscle mass, sarcopenia and osteosarcopenic obesity according to the most recent guidelines. The possible use of adipose indices will be considered, such as the fat mass index (FMI) or the android/gynoid ratio, as well as lipodystrophy indices and the evaluation of visceral adipose tissue (VAT). Whenever available, we will provide possible cut-off diagnostic values for each of these LM and FM indices, according to current literature and guidelines.

A case report of systemic mastocytosis associated with multiple hematologic non-mast cell lineage diseases.

Systemic mastocytosis (SM) is a hematological malignancy characterized by extracutaneous infiltration by atypical mast cells. Together with indolent SM, aggressive SM, and mast cell leukemia, the World Health Organization (WHO) recognizes another major disease subgroup: SM with an associated hematological neoplasm, which is characterized by the presence of a concurrent neoplasm, more commonly, a chronic myelomonocytic leukemia. While KIT D816V is commonly regarded as the driver mutation, the clinical presentation of SM is extremely varied. Treatment of SM might not be simple, but now more specific therapies tailored toward prognostic subgroups of patients have been developed. Here, we report a detailed description of clinical management and biological features of a systemic mastocytocis case associated with multiple hematologic non-mast cell lineage diseases.

Trabecular Bone Score (TBS) and Bone Metabolism in Patients Affected with Type 1 Neurofibromatosis (NF1).

In patients with neurofibromatosis type 1 (NF1), decreased bone mineral density (BMD) and low levels of 25-hydroxy vitamin D3 (25OHD) have been reported. Recently, the trabecular bone score (TBS) measurement has been proposed as index of bone microarchitecture and fracture risk. In 74 NF1 patients (48 females, 26 males, age 41 ± 12), we measured TBS and investigated clinical stage, lifestyle, vitamin D, serum bone turnover markers, vertebral and femoral BMD. A homogenous cohort of 61 healthy subjects was used as control group. TBS was lower in NF1 patients (1.266 ± 0.113 vs. 1.346 ± 0.105) without differences between sexes. No correlations with 25OHD, low exercise, low calcium intake, reduced sun exposure, and number of skin neurofibromas were observed. As expected, hypovitaminosis D was common (98.6%), as well as BMD reduction in hip and spine sites: In NF1 patients, bone texture evaluated by TBS was low in both sexes without any correlation with clinical or metabolic parameters, suggesting a direct role of the fibromin mutation.

Usefulness of bone microarchitectural and geometric DXA-derived parameters in haemophilic patients.

INTRODUCTION: Haemophilia is a recessive X-linked inherited bleeding disorder, whose typical symptom is spontaneous intra-articular haemorrhage leading to joint damage, which can be quantified by the Haemophilia Joint Health Score (HJHS). Arthropathy and other characteristics of haemophilic patients may reduce bone mineral density (BMD), increasing the risk for fragility fractures, which also may occur due to bone quality impairment. AIM: To evaluate bone quantity by BMD and bone quality by Trabecular Bone Score (TBS), bone strain (BS) and hip structural analysis (HSA) in a haemophilic population, and to relate these parameters to general and specific risk factors for osteoporosis and to HJHS. METHODS: Seventy haemophilic patients ≥18 years were enrolled. Densitometric derived lumbar spine and femoral BMD with TBS, BS and HSA were performed. Data regarding risk factors for osteoporosis, presence of arthroprosthesis or arthrodesis were collected, and HJHS was calculated. A Z-score ≤-2.0 defined a low bone mass. RESULTS: Overall, a reduced bone mass was present in 52 patients at the femur and in 38 at the lumbar spine. Lumbar spine BMD, TBS and BS did not correlate with HJHS. HSA bone geometric parameters correlated negatively with HJHS. BMD and HSA correlated with some risk factors for osteoporosis, namely HIV and its therapy, hepatitis C and smoking. CONCLUSIONS: Haemophilic patients showed a reduced BMD at lumbar spine and/or femur. Femoral bone density and geometry correlated with HJHS. The microarchitecture of the trabecular vertebral bone seemed to be not influenced by the haemophilic joint damage.

Erratum to "Diagnostic imaging of osteoporosis and sarcopenia: a narrative review".

[This corrects the article DOI: 10.21037/qims.2018.01.01.].

Diagnostic imaging of osteoporosis and sarcopenia: a narrative review.

Osteoporosis and sarcopenia represent two major health problems with an increasing prevalence in the elderly population. The correlation between these diseases has been widely reported, leading to the development of the term "osteosarcopenia" to diagnose those patients suffering from both diseases. Several imaging methods for the diagnosis and management of osteoporosis exist, with dual-energy X-ray absorptiometry (DXA) being the most commonly used for measuring bone mineral density (BMD). Imaging technique other than DXA is represented by conventional radiography, computed tomography (CT) and ultrasound (US). Similarly, the imaging technologies used to detect loss of skeletal muscle mass in sarcopenia include DXA, CT, US and magnetic resonance imaging (MRI). These methods differ in terms of reliability, radiation exposure and costs. CT and MRI represent the gold standard for evaluating body composition (BC), but are costly and time-consuming. DXA remains the most often used technology for studying BC, being quick, widely available and with low radiation exposure.

Prevalence and type of errors in dual-energy x-ray absorptiometry.

OBJECTIVES: Pitfalls in dual-energy x-ray absorptiometry (DXA) are common. Our aim was to assess rate and type of errors in DXA examinations/reports, evaluating a consecutive series of DXA images of patients examined elsewhere and later presenting to our institution for a follow-up DXA. METHODS: After ethics committee approval, a radiologist retrospectively reviewed all DXA images provided by patients presenting at our institution for a new DXA. Errors were categorized as patient positioning (PP), data analysis (DA), artefacts and/or demographics. RESULTS: Of 2,476 patients, 1,198 had no previous DXA, while 793 had a previous DXA performed in our institution. The remaining 485 (20 %) patients entered the study (38 men and 447 women; mean age ± standard deviation, 68 ± 9 years). Previous DXA examinations were performed at a total of 37 centres. Of 485 reports, 451 (93 %) had at least one error out of a total of 558 errors distributed as follows: 441 (79 %) were DA, 66 (12 %) PP, 39 (7 %) artefacts and 12 (2 %) demographics. CONCLUSIONS: About 20 % of patients did not undergo DXA at the same institution as previously. More than 90 % of DXA presented at least one error, mainly of DA. International Society for Clinical Densitometry guidelines are very poorly adopted. KEY POINTS: • More than 90 % of DXA examinations/reports presented one or more errors. • About 80 % of errors are related to image data analysis. • Errors in DXA examinations may have potential implications for patients' management.

Managing osteoporosis in ulcerative colitis: something new?

The authors revise the latest evidence in the literature regarding managing of osteoporosis in ulcerative colitis (UC), paying particular attention to the latest tendency of the research concerning the management of bone damage in the patient affected by UC. It is wise to assess vitamin D status in ulcerative colitis patients to recognize who is predisposed to low levels of vitamin D, whose deficiency has to be treated with oral or parenteral vitamin D supplementation. An adequate dietary calcium intake or supplementation and physical activity, if possible, should be guaranteed. Osteoporotic risk factors, such as smoking and excessive alcohol intake, must be avoided. Steroid has to be prescribed at the lowest possible dosage and for the shortest possible time. Moreover, conditions favoring falling have to been minimized, like carpets, low illumination, sedatives assumption, vitamin D deficiency. It is advisable to assess the fracture risk in all UC patient by the fracture assessment risk tool (FRAX(®) tool), that calculates the ten years risk of fracture for the population aged from 40 to 90 years in many countries of the world. A high risk value could indicate the necessity of treatment, whereas a low risk value suggests a follow-up only. An intermediate risk supports the decision to prescribe bone mineral density (BMD) assessment and a subsequent patient revaluation for treatment. Dual energy X-ray absorptiometry bone densitometry can be used not only for BMD measurement, but also to collect data about bone quality by the means of trabecular bone score and hip structural analysis assessment. These two indices could represent a method of interesting perspectives in evaluating bone status in patients affected by diseases like UC, which may present an impairment of bone quality as well as of bone quantity. In literature there is no strong evidence for instituting pharmacological therapy of bone impairment in UC patients for clinical indications other than those that are also applied to the patients with osteoporosis. Therefore, a reasonable advice is to consider pharmacological treatment for osteoporosis in those UC patients who already present fragility fractures, which bring a high risk of subsequent fractures. Therapy has also to be considered in patients with a high risk of fracture even if it did not yet happen, and particularly when they had long periods of corticosteroid therapy or cumulative high dosages. In patients without fragility fractures or steroid treatment, a medical decision about treatment could be guided by the FRAX tool to determine the intervention threshold. Among drugs for osteoporosis treatment, the bisphosphonates are the most studied ones, with the best and longest evidence of efficacy and safety. Despite this, several questions are still open, such as the duration of treatment, the necessity to discontinue it, the indication of therapy in young patients, particularly in those without previous fractures. Further, it has to be mentioned that a long-term bisphosphonates use in primary osteoporosis has been associated with an increased incidence of dramatic side-effects, even if uncommon, like osteonecrosis of the jaw and atypical sub-trochanteric and diaphyseal femoral fractures. UC is a long-lasting disease and the majority of patients is relatively young. In this scenario primary prevention of fragility fracture is the best cost-effective strategy. Vitamin D supplementation, adequate calcium intake, suitable physical activity (when possible), removing of risk factors for osteoporosis like smoking, and avoiding falling are the best medical acts.

Bone quality, as measured by trabecular bone score, in patients with primary hyperparathyroidism.

OBJECTIVE: In primary hyperparathyroidism (PHPT), vertebral fractures (VFx) occur regardless of bone mineral density (BMD) and may depend on decreased bone quality. Trabecular bone score (TBS) is a texture measurement acquired during a spinal dual-energy X-ray absorptiometry (DXA). Recently, TBS has been proposed as an index of bone micro-architecture. DESIGN: We studied 92 PHPT patients (74 females, age 62.1±9.7 years) and 98 control subjects. In all patients at baseline, in 20 surgically treated patients and in 10 conservatively treated patients after 24 months, TBS, spinal (lumbar spine (LS)) and femoral (total hip (TH) and femoral neck (FN)) BMD were assessed by DXA and VFx by spinal radiograph. RESULTS: PHPT patients had lower TBS (-2.39±1.8) and higher VFx prevalence (43.5%) than controls (-0.98±1.07 and 8.2% respectively, both P<0.0001). TBS was associated with VFx (odds ratio 1.4, 95% CI 1.1-1.9, P=0.02), regardless of LS-BMD, age, BMI and gender, and showed a better compromise between sensitivity (75%) and specificity (61.5%) for detecting VFx than LS-BMD, TH-BMD and FN-BMD (31 and 75%, 72 and 44.2%, and 64 and 65% respectively). In surgically treated patients, TBS, LS-BMD, TH-BMD and FN-BMD increased (+47±44.8,+29.2±34.1,+49.4±48.7 and +30.2±39.3% respectively, all P<0.0001). Among patients treated conservatively, TBS decreased significantly in those (n=3) with incident VFx (-1.3±0.3) compared with those without (-0.01±0.9, P=0.048), while BMD changes were not statistically different (LS 0.3±1.2 vs -0.8±0.9 respectively, P=0.19; TH 0.4±0.8 vs -0.8±1.4 respectively, P=0.13 and FN 0.4±0.9 vs -0.8±1.4 respectively, P=0.14). CONCLUSIONS: In PHPT, bone quality, as measured by TBS, is reduced and associated with VFx and improves after surgery.

Dose absorption in lumbar and femoral dual energy X-ray absorptiometry examinations using three different scan modalities: an anthropomorphic phantom study.

The aim of this study was to measure the effective dose on an anthropomorphic phantom undergoing lumbar and femoral dual energy X-ray absorption (DXA) examinations, using 3 different scan modalities (fast-array [FA], array [A], high-definition [HD]), and assess the differences in the lifetime attributable risk (LAR) of cancer due to radiation. An anthropomorphic phantom was used. Thermoluminescent dosimeters were placed over 12 anatomic phantom regions and outside the room (to measure background radiation). Fifty scans on the femur and spine were performed for each mode. The dose relative to a single DXA scan for each dosimeter was measured (mean over the 50 scans) and the background radiation was then subtracted. The equivalent dose per organ was obtained. The total body effective dose was calculated by adding the equivalent doses. We estimated the lifetime dose absorption and LAR for cancer for a male and a female patient undergoing 36 DXA studies (18 lumbar, 18 femoral) every 21 months for 32 years. The effective dose for lumbar scans was FA = 17.79 µSv, A = 32.88 µSv, HD = 31.08 µSv; for femoral scans, FA = 5.29 µSv, A = 9.55 µSv, HD = 7.54 µSv. LAR estimation showed a minimal increase in cancer risk (range 4.55 × 10⁻4% [FA, femoral, male] to 4.02 × 10⁻³% [A, lumbar, female]). The lifetime dose absorption and LAR for cancer for a male and a female patient undergoing 36 DXA studies (18 lumbar, 18 femoral) every 21 months for 32 years were 0.756 mSv, 3.82 × 10(-3)% and 0.756 mSv, 5.11 × 10⁻³%, respectively. DXA examinations cause radiation levels that are comparable to the background radiation. Regardless of the scan modality or the anatomic site, a patient undergoing DXA scans for a lifetime has a negligible increased risk of developing cancer.

Bone quality, as measured by trabecular bone score in patients with adrenal incidentalomas with and without subclinical hypercortisolism.

Patients with adrenal incidentalomas (AIs) and subclinical hypercortisolism (SH) have increased risk of fracture independent of bone mineral density (BMD) and possibly due to reduced bone quality. The trabecular bone score (TBS) has been proposed as a index of bone microarchitecture. The aim of the study was to investigate TBS in AI. In 102 AI patients, SH was diagnosed in the presence of at least two of the following: (1) urinary free cortisol >70 µg/24 h (193.1 nmol/L); (2) cortisol after 1-mg dexamethasone suppression test (1-mg DST) >3.0 µg/dL (82.8 nmol/L); or (3) adrenocorticotropic hormone (ACTH) <10 pg/mL (<2.2 pmol/L). In patients and in 70 matched controls, BMD was measured at lumbar spine (LS) and femur (neck [FN] and total [FT]) by dual X-ray absorptiometry and TBS was assessed in the region of LS-BMD; BMD and TBS data were reported as Z-scores. In patients, vertebral deformities were assessed by radiograph. Patients with SH (n = 34) had lower LS-BMD (-0.31 ± 1.17), FT-BMD (-0.29 ± 0.91), and TBS (-3.18 ± 1.21) than patients without SH (n = 68, 0.31 ± 1.42, p = 0.03; 0.19 ± 0.97, p = 0.01; -1.70 ± 1.54, p < 0.0001, respectively) and controls (0.42 ± 1.52, p = 0.02; 0.14 ± 0.76, p = 0.02; -1.19 ± 0.99, p < 0.0001, respectively). TBS was inversely correlated with 1-mg DST (ß = -0.26, t = -2.79, p = 0.006) regardless of age, LS-BMD, body mass index (BMI), and gender. The presence of fracture was associated with low TBS alone (odds ratio [OR], 4.8; 95% confidence interval [CI], 1.85-12.42, p = 0.001) and with the cluster low TBS plus low LS-BMD (OR, 4.37; 95% CI, 1.71-11.4, p = 0.002), after adjustment for age, BMI, and gender. Low TBS plus low LS-BMD showed a good specificity (79%) for predicting fractures, whereas normal TBS (ie, > -1.5) plus normal LS-BMD high specificity (88.1%) for excluding fractures. Finally, TBS predicted the occurrence of a new fracture in 40 patients followed for 24 months (OR, 11.2; 95%CI, 1.71-71.41, p = 0.012) regardless of LS-BMD, BMI, and age. In SH, bone quality, as measured by TBS, is altered. TBS is useful in detecting AI patients at risk of fractures.

Back pain treatment in post-menopausal osteoporosis with vertebral fractures.

Chronic back pain is frequent in osteoporotic patients with multiple fractures, and increases after subsequent findings of new vertebral fractures. Both acute and chronic back pain improve during pharmacological treatment for osteoporosis, but the efficicacy is different among drugs. Patients affected by osteoporosis treated with antiresorptive and anabolic agents have a reduced risk of new or worsening back pain, particularly with teriparatide therapy. Teriparatide reduces back pain and improves quality of life in post-menopausal osteoporosis with vertebral fractures more than other drugs.