A practical approach for anabolic treatment of bone fragility with romosozumab.

BACKGROUND: Romosozumab, a fully humanized anti-sclerostin-antibody, is a bone-builder stimulating osteoblasts and inhibiting osteoclast by activation of the canonical Wnt-beta catenin signaling. This unique mechanism of action has the potential to address unmet needs in osteoporosis management. METHODS: The multifaceted practical clinical issues related to romosozumab are discussed, especially focusing on the rationale of employing a sclerostin inhibitor to target bone fragility as first line or second line treatment in post-menopausal osteoporosis and in males at increased risk of fractures. RESULTS: Four randomized clinical trials with several post-hoc analyses and more than ten observational studies have consistently demonstrated that romosozumab is effective in rapidly increasing bone mineral density (BMD) and decreasing risk of vertebral, non-vertebral and hip fractures in post-menopausal women at very-high risk of fractures. In male osteoporosis, only data on BMD are available. Noteworthy, romosozumab was shown to be more effective and rapid than teriparatide in improving BMD, bone structure and strength at the hip, especially in women already treated with anti-resorptive drugs. Interestingly, even if romosozumab displays best results in treatment-naïve patients, its favourable effects on BMD were observed even in women previously treated with teriparatide or denosumab, although to a lesser extent. CONCLUSIONS: Based on the available evidence, romosozumab could be proposed as ideal drug in several clinical settings, such as non-fractured post-menopausal women at very-high risk of fractures, patients with recent hip fracture, patients non responder to bisphosphonates and short-term denosumab therapy.

Presentation of hypoparathyroidism in Italy: a nationwide register-based study.

PURPOSE: We sought to assess the clinical presentation of hypoparathyroidism (HypoPT) in Italy. METHODS: We performed a nationwide study retrieving data from the hospital discharge ICD-9 codes database of the Italian Health Ministry, from 2007 through 2017. The codes corresponding to diagnosis of cardiovascular disease, cancer, infection, renal failure, psychiatric disease, upper airway tract infection and pneumonia, seizures, nephrolithiasis, cognitive impairment, cerebral calcifications, skin disorders, fracture, and cataract were retrieved when associated with the diagnosis of HypoPT (252.1). We excluded codes corresponding to diagnoses of cancer of the neck region. In-hospital mortality rate was calculated. We retrieved the same data from an age- and sex-matched non-HypoPT control population. RESULTS: Fourteen thousand five hundred seventy-nine hospitalizations for HypoPT and controls were analyzed. Hospitalization for cardiovascular disease, cancer, infection, renal failure, seizures, nephrolithiasis, cerebral calcifications (p < 0.0001), and cognitive impairment (p < 0.05) were more common in HypoPT compared to controls. Mean age of HypoPT with cardiovascular disease, cancer, and renal failure was younger compared to controls (p < 0.0001). The OR of hospitalization for cardiovascular disease, cancer, renal failure, seizures (OR 2, 40, 48  and 1.6, respectively), and nephrolithiasis (OR 1.6) were significant in HypoPT compared to non-HypoPT. The OR of hospitalization for infection and cognitive impairment were significant only in HypoPT women (OR 1.3 and 2.3, respectively). In-hospital mortality rate was lower in HypoPT vs controls (0.5% and 3.7%; p < 0.0001). CONCLUSION: Hospitalizations for cardiovascular disease, cancer, and renal failure are more prevalent and occur at a younger age in HypoPT vs non-HypoPT. Hospitalizations for seizures and nephrolithiasis are frequent in HypoPT; those for infection and cognitive impairment are more common in HypoPT women.

Twenty-four hour Holter ECG in normocalcemic and hypercalcemic patients with hyperparathyroidism.

PURPOSE: To investigate the occurrence of arrhythmias in patients with normocalcemic (NC) primary hyperparathyroidism (PHPT) compared to both hypercalcemic PHPT patients and control subjects by means of 24-h Holter ECG. METHODS: Thirteen NCPHPT postmenopausal patients were enrolled and age-matched with 13 hypercalcemic PHPT patients and 13 controls. Every subject underwent basal ECG, 24-h Holter ECG and mineral metabolism biochemical evaluation. RESULTS: PHPT patients had higher mean serum calcium levels compared to both NCPHPT and controls; there was no difference in mean serum calcium levels between NCPHPT and controls. Both NCPHPT and PHPT patients had significantly higher mean PTH levels compared with controls. There were no differences in ECG parameters between the three groups, except for QTc interval. PHPT patients had normal QTc interval values, but significantly shorter mean values compared with those of controls and NCPHPT patients. During 24-h Holter ECG recording, 100% of PHPT patients had supraventricular premature beats (SVPBs), compared to 46% of NCPHPT (p = 0.005) and to 53% of controls (p = 0.01). PHPT patients experienced ventricular premature beats (VPBs) (69.2%) vs 15% of NCPHPT patients (p = 0.01) and 23% of controls (p = 0.04). There was no difference between NCPHPT and controls subjects concerning occurrence of both VPBs and SVPBs. CONCLUSIONS: NCPHPT patients did not experience an increased occurrence of arrhythmias compared to controls, while PHPT patients showed an increased occurrence compared to both controls and NCPHPT. Our findings are most probably related to the short QTc interval caused by hypercalcemia observed in PHPT patients, but not in NCPHPT.

A Wearable Device for Hand Sensorimotor Rehabilitation Through Augmented Sensory Feedback.

The loss of sensitivity of the upper limb due to central or peripheral neurological injuries severely limits the ability to manipulate objects, hindering personal independence. Non-invasive augmented sensory feedback techniques are used to promote neural plasticity hence to restore the grasping function. We devised a wearable device for hand sensorimotor rehabilitation capable of reliably detect transient tactile events based on custom piezoelectric polyvinylidene fluoride (PVDF) sensors and deliver discrete bursts of vibrations upon these events. We integrated the sensors into a fabric glove and tested the device in a pilot bench test exploring its ability to detect object contact and release as well as object slippage. Due to their broad bandwidth, the sensors proved to be suitable for both the applications: they responded with clear peaks when touching or releasing the object and increased the high-frequency content of the signal during slippage.

Study of the link between hemotopoietic and skeletal systems in patients attending a referral center for osteoporosis.

PURPOSE: To investigate the link between hematopoietic and skeletal tissues in patients with fragility fractures. METHODS: We retrospectively analyzed the medical records of women older than 40 years who attended the Bone Disease Unit of "Sapienza" University of Rome for their first visit for osteoporosis from January 2020 to June 2022. RESULTS: Fragility fractures were found in 61.8% of the sample. In particular, vertebral fractures in 35.5%, femoral fractures in 6.3%, Colles fractures in 16.5% and non-vertebral non-hip in 42.5%. Fractured patients were significantly older compared to non-fractured, had lower mean values of lumbar spine (p = 0.01), and femoral neck BMD (p = 0.007). A red blood cell distribution width (RDW) value higher than 15% was observed four times more in those with fractures compared to non-fractured patients (8.9% vs 2%, p = 0.01) and was associated with vertebral fracture after adjusting for age, BMI, menopause, nutritional status, smoking, osteoporosis and anemia (OR = 4.1, 95% CI 1.6-11.4, p = 0.003). Hematocrit was negatively associated with hip fracture also adjusting for age, BMI, menopause, nutritional status, smoking, osteoporosis (p = 0.025). CONCLUSION: Our study demonstrates that RDW values were significantly associated with vertebral fracture and hematocrit with hip fracture. Since both parameters are included in the initial evaluation of patients with suspected bone fragility, our results should push doctors to look at these values with no incremental cost for national health services.

Bone quality in endocrine diseases: determinants and clinical relevance.

PURPOSE: Bone is one of the main targets of hormones and endocrine diseases are frequent causes of secondary osteoporosis and fractures in real-world clinical practice. However, diagnosis of skeletal fragility and prediction of fractures in this setting could be a challenge, since the skeletal alterations induced by endocrine disorders are not generally captured by dual-energy X-ray absorptiometry (DXA) measurement of bone mineral density (BMD), that is the gold standard for diagnosis of osteoporosis in the general population. The aim of this paper is to review the existing evidence related to bone quality features in endocrine diseases, proposing assessment with new techniques in the future. METHODS: A comprehensive search within electronic databases was performed to collect reports of bone quality in primary hyperparathyroidism, hypoparathyroidism, hyperthyroidism, hypercortisolism, growth hormone deficiency, acromegaly, male hypogonadism and diabetes mellitus. RESULTS: Using invasive and non-invasive techniques, such as high-resolution peripheral quantitative computed tomography or DXA measurement of trabecular bone score (TBS), several studies consistently reported altered bone quality as predominant determinant of fragility fractures in subjects affected by chronic endocrine disorders. CONCLUSIONS: Assessment of skeletal fragility in endocrine diseases might take advantage from the use of techniques to detect perturbation in bone architecture with the aim of best identifying patients at high risk of fractures.

The role of preoperative prostatic shape in the recovery of urinary continence after robotic radical prostatectomy: a single cohort analysis.

BACKGROUND: To explore the role of preoperative MRI prostate shape in urinary incontinence after robot-assisted radical prostatectomy (RARP). METHODS: Patients were stratified into four groups based on the mpMRI prostatic apex shape: Group A (prostatic apex overlapping the membranous urethra anteriorly and posteriorly), Group B and C (overlap of the prostatic apex of the anterior or posterior membranous urethra, respectively) and Group D (no overlap). Preoperative variables and intraoperative data were compared. Continence recovery was defined as no pad/day or 1 safety pad/day by an outpatient evaluation performed at 1, 3, 6, and 12 months after RARP. RESULTS: One hundred patients underwent RARP were classified as belonging to Group A (n = 30), Group B (n = 16), Group C (n = 14), and Group D (n = 40). Group D showed a significantly more favorable urinary continence recovery after RARP respect to all the other shapes presenting any forms of overlapping (HR = 1.9, 95% CI 1.2-3.1, p = 0.007). The estimated HR remained substantially unchanged after adjusting by age, body mass index, CCI, prostate volume, and bladder neck sparing (HR = 1.9, 95% CI 1.1-3.2, p = 0.016). The continence recovery median time was 9 months for Group A + B + C (95% CI 5-11) and 4 months for Group D (95% CI 2-6) (p = 0.023). CONCLUSION: Shape D showed a better continence recovery when compared to other shapes presenting any kind of overlapping of the prostatic apex over the membranous urethra.

The myokinetic stimulation interface: activation of proprioceptive neural responses with remotely actuated magnets implanted in rodent forelimb muscle.

Objective. Proprioception is the sense of one's position, orientation, and movement in space, and it is of fundamental importance for motor control. When proprioception is impaired or absent, motor execution becomes error-prone, leading to poorly coordinated movements. The kinaesthetic illusion, which creates perceptions of limb movement in humans through non-invasively applying vibrations to muscles or tendons, provides an avenue for studying and restoring the sense of joint movement (kinaesthesia). This technique, however, leaves ambiguity between proprioceptive percepts that arise from muscles versus those that arise from skin receptors. Here we propose the concept of a stimulation system to activate kinaesthesia through the untethered application of localized vibration through implanted magnets.Approach. In this proof-of-concept study, we use two simplified one-DoF systems to show the feasibility of eliciting muscle-sensory responses in an animal model across multiple frequencies, including those that activate the kinaesthetic illusion (70-115 Hz). Furthermore, we generalized the concept by developing a five-DoF prototype system capable of generating directional, frequency-selective vibrations with desired displacement profiles.Main results. In-vivotests with the one-DoF systems demonstrated the feasibility to elicit muscle sensory neural responses in the median nerve of an animal model. Instead,in-vitrotests with the five-DoF prototype demonstrated high accuracy in producing directional and frequency selective vibrations along different magnet axes.Significance. These results provide evidence for a new technique that interacts with the native neuro-muscular anatomy to study proprioception and eventually pave the way towards the development of advanced limb prostheses or assistive devices for the sensory impaired.

Assessing value of contrast-enhanced ultrasound vs. conventional transthoracic ultrasound in improving diagnostic yield of percutaneous needle biopsy of peripheral lung lesions.

OBJECTIVE: The aim of the present study was to systematically assess the value of contrast-enhanced ultrasound (CEUS) vs. conventional transthoracic ultrasound (TUS) in improving diagnostic accuracy of percutaneous needle biopsy (PTNB) for subpleural lung lesions. PATIENTS AND METHODS: 232 patients with subpleural lesions were 1:1 randomly assigned to a group were CEUS was performed (n=116, mean age=65.5±5.6, M=69) or not (n=116, mean age=66.0±5.3, M=70). For CEUS study was used an injection of 4.8 mL of SonoVue (Bracco, Italy). For PTNB was employed a Menghini-modified technique with a semi-automatic 18-gauge needle. RESULTS: The mean diameter of subpleural lesions was 2.85±0.7 cm in the CEUS+ group and 2.95±0.6cm in the CEUS- group. Only 3 lesions, 1 in the CEUS+ group and 2 in the CEUS- group measured >5 cm. CEUS showed no superiority in terms of diagnostic accuracy compared to conventional TUS (p=0.34). Similar results were obtained in the sub-analysis of lesions sized between 1-2 cm (p=1.00) and 2-5 cm (p=0.08). As the lesion size increased, the detection rate of necrosis in lesions increased by CEUS (from 8% to 31%). CEUS showed no superiority in terms of diagnostic accuracy in the sub-analysis of necrotic lesions at CECT (p=0.38). AUC values for both the groups assessed an excellent diagnostic yield for TUS-PTNB (≥0.80). CONCLUSIONS: CEUS study does not improve the diagnostic accuracy of TUS-guided PTNB for peripheral lung lesions <5 cm of diameter. Further studies evaluating CEUS guidance for larger (>5 cm) and necrotic lesions are needed prior that its potential can be clarified.

Is thulium laser vapoenucleation of the prostate equally safe and effective in elderly patients? A propensity score matched analysis of early perioperative and functional outcomes. / Vapoenucleación prostática con láser Tulio. ¿Es igual de segura y efectiva en pacientes ancianos? Análisis por puntuación de propensión de los resultados funcionales y perioperatorios tempranos.

PURPOSE: To evaluate if thulium laser vapoenucleation of the prostate (ThuVEP) is equally safe and effective in a selected cohort of elderly patients when compared to "younger" patients. MATERIALS AND METHODS: We performed a retrospective analysis of consecutive patients who underwent ThuVEP between September 2018 and February 2020. After application of the inclusion/exclusion criteria, patients were stratified according to the 75 years-old cut-off point suggested by the WHO. Group A included patients < 75 years-old; Group B included patients > 75 years-old. Preoperative assessment included urological consultation, prostate specific antigen (PSA), International Prostate Symptom Score (IPSS) and quality of life index, transrectal ultrasound to estimate prostate volume (PVol), and uroflowmetry to assess preoperative Qmax, Qave and post-void residual volume (PVR). Perioperative and postoperative data were analyzed during 3-month follow-up. RESULTS: After propensity-score analysis, 51 versus 51 patients were 1:1 matched according to PVol, PSA, Qmax, IPSS and QoL. Patients were comparable at baseline excluding age (65 (IQR 59-70) versus 79 (IQR 77-82) years, Group A versus B, respectively, p-value < 0.001). No differences were found in terms of hemoglobin drop, complications rate, catheterization time and length of hospital stay. Group A (younger) patients had more significant improvement in 30-days absolute Qmax, Qave and ΔQmax. At 90-days follow-up, the differences between the groups disappeared. Within the 90-days follow-up, no significant differences were found in the readmission rate, with no need of reinterventions. CONCLUSIONS: In our hands, even in elderly patients affected by BPH, ThuVEP appears to be a safe and effective treatment option.

Higher serum levels of a cathepsin K-generated periostin fragment are associated with fractures in postmenopausal women with primary hyperparathyroidism: a pilot study.

The only difference between fractured and non-fractured postmenopausal women with PHPT of same sex, age, and BMI was a significantly mean higher serum k-periostin level. K-periostin value was associated with fracture at any site (odds ratio 1.044, 95% CI 1.005-1.091, p = 0.03). INTRODUCTION: To assess serum k-periostin fragment levels in patients with primary hyperparathyroidism (PHPT), fractured and non-fractured matched for sex, age, and body mass index. METHODS: Twenty-five Caucasian fractured postmenopausal women with PHPT (group Fx) and 25 PHPT non-fractured (group NFx) were enrolled. Each patient underwent DXA scan at lumbar, hip, and forearm, spine X-ray, and biochemical evaluation of calcium metabolism. For k-periostin analyses, we utilized a specific ELISA test that detects CatK-generated fragment levels in the bloodstream. RESULTS: We found no difference in mean BMD and bone turnover marker values between Fx and NFx groups. Prevalence of osteoporosis was not significantly different in Fx vs NFx (72% vs 60%, p = 0.55). Among Fx, 16% reported multiple fractures, 28% morphometric vertebral fractures, 4% femoral fractures, 28% non-vertebral non-femoral fractures, and 8% wrist fractures. The only detectable difference between Fx and NFx group was a significantly mean higher k-periostin serum level (46.2 ± 21.4 vs 34.7 ± 13.5 ng/ml, p = 0.02). K-periostin was associated with fracture at any site (odds ratio 1.044, 95% CI 1.005-1.091, p = 0.03). No difference in mean k-periostin values was found between patients with vertebral fracture vs those with non-vertebral fracture, and between those with multiple fractures vs those with single fracture. CONCLUSION: Serum k-periostin is significantly associated with fracture in PHPT. If confirmed by further studies, k-periostin could be considered a new marker of bone fragility in PHPT, independently of BMD.

Lumbar spine bone mineral density and trabecular bone score-adjusted FRAX, but not FRAX without bone mineral density, identify subclinical carotid atherosclerosis.

PURPOSE: Osteoporosis and atherosclerosis share common risk factors. Aim of this study was to test if FRAX (which is an algorithm that can identify subjects at risk of fracture), without or with BMD values, also adjusted for trabecular bone score (TBS) was able to identify subclinical atherosclerosis, evaluated by measurement of carotid intima media thickness (cIMT ≥ 0.9 mm) as compared to DXA values. METHODS: Ninety postmenopausal women underwent DXA measurement and cIMT evaluation. For each patient, the FRAX algorithm for major osteoporotic fracture (M) and for hip fracture (H) without BMD was computed, together with FRAX with BMD and TBS-adjusted FRAX. Serum levels of osteoprotegerin, sRANKL, and interleukin-6 were also measured. RESULTS: There were no differences in anthropometric parameters and cardiovascular risk factors between subjects with cIMT ≥ 0.9 mm (35% of subjects, group A) compared to those with cIMT < 0.9 mm (group B). The prevalence of osteoporosis and FRAX BMD, TBS-adjusted FRAX both for M and H were higher in group A compared to group B. The best ROC curves to identify subjects with a cIMT ≥ 0.9 mm were: lumbar spine T-score, with a threshold of - 2.5 SD (area under the curve, AUC 0.64; p = 0.02) with a sensibility of 50% and a specificity of 76%; TBS-adjusted FRAX H with a sensibility of 50% and a specificity of 72% (AUC 0.64; p = 0.01 with a threshold of 3%). Interleukin-6 positively correlated with FRAX BMD H and M. CONCLUSIONS: FRAX without BMD does not identify subclinical carotid atherosclerosis, while lumbar spine T-score and TBS-adjusted FRAX H similarly detected it with higher specificity for T-score.

Diagnostic pathway of the biopsy-naïve patient suspected for prostate cancer: Real-life scenario when multiparametric Magnetic Resonance Imaging is not centralized.

INTRODUCTION: We aimed to compare the pathway including multi-parametric Magnetic Resonance Imaging (mpMRI) versus the one without mpMRI in detection of prostate cancer (PCa) when mpMRI is not centralized. MATERIALS: January 2019-March 2020: prospective data collection of trans-perineal prostate biopsies. Group A: biopsy-naïve patients who underwent mpMRI (at any institution) versus Group B: patients who did not. Within Group A, patients were stratified into those with negative mpMRI (mpMRI-, PIRADS v2.1=1-3, with PSA density <0.15 if PIRADS 3) who underwent standard biopsy (SB), versus those with positive mpMRI (mpMRI+, when PIRADS 3-5, with PSA density>0.15 if PIRADS 3) who underwent cognitive fusion biopsy. RESULTS: Two hundred and eighty one biopsies were analyzed. 153 patients underwent mpMRI (Group A). 98 mpMRI+ underwent fusion biopsy; 55 mpMRI- underwent SB. 128 Group B patients underwent SB. Overall PCa detection rate was 52.3% vs. 48.4% (Group A vs. B, P=0.5). Non-clinically-significant PCa was detected in 7.8 vs. 13.3% (Group A vs. B, P=0.1). Among the 98 mpMRI+ Group A patients only 2 had non clinically-significant disease. In 55 mpMRI- patients who underwent SB, 10 (18.2%) had clinically-significant PCa. Prostate volume predicted detection of PCa. In Group B, age and PSA predicted PCa. Sensitivity of mpMRI was 75.0% for all PCa, 85.3% for clinically-significant PCa. CONCLUSION: Higher detection of PCa and lower detection of non-clinically-significant PCa favored mpMRI pathway. A consistent number of clinically-significant PCa was diagnosed after a mpMRI-. Thus, in real-life scenario, mpMRI- does not obviate indication to biopsy when mpMRI is not centralized. LEVEL OF EVIDENCE: 3.

Vertebral fracture assessment (VFA) for monitoring vertebral reshaping in children and adolescents with osteogenesis imperfecta treated with intravenous neridronate.

PURPOSE: The study was aimed at monitoring vertebral bodies changes with the use of Vertebral Fracture Assessment (VFA) in children and adolescents affected by osteogenesis imperfecta (OI) during treatment with intravenous neridronate. METHODS: 60 children and adolescents (35 males and 25 females; age 1-16 years) with OI type I, III and IV were included in the study. Intravenous neridronate was administered at the dose of 2 mg/kg every 3 months in all patients. Lumbar spine (LS) bone mineral density (BMD) and VFA by dual X-ray absorptiometry (DXA) were assessed every 6 months up to 24 months during treatment. VFA with vertebral morphometry (MXA) was used to calculate the three indices of vertebral deformity: wedging, concavity and crushing. Serum calcium, phosphate, parathyroid hormone (PTH), 25-hydroxy-vitamin D [25(OH)D], total alkaline phosphatase (ALP), bone alkaline phosphatase (BALP) and urinary C-terminal telopeptide of type 1 collagen (CTx) were measured at any time point. RESULTS: Mean LS BMD values significantly increased at 24 months compared to baseline (p < 0.0001); the corresponding Z-score values were -1.28 ± 1.23 at 24 months vs -2.46 ± 1.25 at baseline; corresponding mean Bone Mineral Apparent Density (BMAD) values were 0.335 ± 0.206 vs 0.464 ± 0.216. Mean serum levels of ALP, BALP and CTx significantly decreased from baseline to 24 months. By MXA, we observed a significant 19.1% reduction of the mean wedging index of vertebral reshaping at 12 months, and 38.4% at 24 months (p < 0.0001) and of the mean concavity index (16.3% at 12 months and 35.9% at 24 months; p < 0.0001). Vertebral reshaping was achieved for 66/88 (75%) wedge fractures and 59/70 (84%) concave fractures, but there were 4 incident mild fractures. Finally, VF rate was reduced at 24 months compared to baseline: 37/710 (5.2%) vs 158/710 (22.2%). CONCLUSION: Our study demonstrates the utility of VFA as a safe and alternative methodology in the follow-up of children and adolescents with OI.

'Doublecheck: a sensory confirmation is required to own a robotic hand, sending a command to feel in charge of it'.

Over a lifetime of experience, the representation of the body is built upon congruent integration of multiple elements constituting the sensorimotor loop. To investigate its robustness against the rupture of congruency between senses and with motor command, we selectively manipulated in healthy subjects the binds between sight, proprioception, and efferent motor command. Two experiments based on the Moving Hand Illusion were designed employing Tendon Vibration Illusion to modulate proprioception and generate illusory altered feedback of movement. In Experiment A, visuomotor congruency was modulated by introducing adelay between complex multifingered movements performed by arobotic hand and real movement of each participant's hand. In the presence of the motor command, visuomotor congruency enhanced ownership, agency, and skin conductance, while proprioceptive-motor congruency was not effective, confirming the prevalence of vision upon proprioception. In Experiment B, the impact of visuo-proprioceptive congruency was tested in the absence of motor command because the robotic hand moved autonomously. Intersensory congruency compensated for the absence of motor command only for ownership. Skin conductance in Exp Band Proprioceptive Drift in both experiments did not change. Results suggest that ownership and agency are independently processed, and presence of the efferent component modulates sensory feedbacks salience. The brain seems to require the integration of at least two streams of congruent information. Bodily awareness can be generated from sensory information alone, but to feel in charge of the body, senses must be double-checked with the prediction generated from efference copy, which is treated as an additional sensory modality.

Vitamin D screening.

At present, there is no need and no sufficient evidence to support universal screening for vitamin D status. There are four categories of subjects in whom there is no requirement for screening, since a number of studies indicate beneficial effects of vitamin D supplementation; these are represented by children and adolescents, pregnant women, patients taking bone active drugs and subjects with documented hypovitaminosis D. In the remaining subjects, the utilization of adequate questionnaires will target with sufficient sensitivity and specificity those with hypovitaminosis D. These must be first supplemented and, at a later time, serum 25(OH)D assay should be requested to confirm attainment of sufficiency, independently of the threshold chosen. This strategy will cut costs deriving from both widespread use of vitamin D assays and vitamin D supplementation.

Long-term bone mineral density changes after surgical cure of patients with tumor-induced osteomalacia.

This paper reports our personal experience filling the gap regarding changes of bone mineral density after surgical treatment in patient suffering from tumor-induced osteomalacia. INTRODUCTION: No systematic data are available regarding long-term bone mineral density (BMD) changes after surgical cure of patients with tumor-induced osteomalacia. METHODS: From October 2001 through April 2018, we studied 10 consecutive patients (mean age ± SD, 45.5 ± 13.8 years; 5 males and 5 females) with tumor-induced osteomalacia. We evaluated BMD when initially presented at our Center and after surgical removal of the tumor. RESULTS: Basal BMD and corresponding Z-score values (mean values ± SD) measured by DXA were as follows: L1-L4 = 0.692 ± 0.15 g/cm2, Z-score = - 2.80 ± 1.60; femur neck 0.447 ± 0.10 g/cm2, Z-score = - 2.66 ± 0.93; total femur = 0.450 ± 0.08 g/cm2, Z-score = -3.04 ± 0.85). Furthermore, Trabecular Bone Score (TBS) was evaluated in three patients (basal values, 0.990 ± 0.32). Seven patients were intermittently followed after surgical excision of the tumor while supplemented with cholecalciferol and calcium salts; the remaining three were lost to follow-up. There was a striking increase of BMD values that peaked at 26.7 ± 6.50 months: L1-L4 = 1.289 ± 0.247 g/cm2, p < 0.001, Z-score + 1.75 ± 1.42; femur neck = 0.890 ± 0.235 g/cm2, p = 0.028, Z-score = + 0.50 ± 1.40; total femur = 0.834 ± 0.150 g/cm2, p = 0.005, Z-score = - 0.74 ± 1.14. In patients with the greatest bone involvement at lumbar site, there was a striking increase of an average 1.5% (p < 0.01) in respect to baseline Z-score value for each additional month of observation during the first 2-3 years post-surgery. An improvement of trabecular microarchitecture was also documented (TBS, 1.255 ± 0.16). CONCLUSION: This is the first case series documenting an impressive increase of BMD at both lumbar and femoral sites, together with an improvement of trabecular microarchitecture as documented by TBS. This is the consequence of huge mineralization of the large amount of osteoid tissue after resolution of the disease.