Radiological diagnosis of prevalent osteoporotic vertebral fracture on radiographs: an interim consensus from a group of experts of the ESSR osteoporosis and metabolism subcommittee.

When a low-energy trauma induces an acute vertebral fracture (VF) with clinical symptoms, a definitive diagnosis of osteoporotic vertebral fracture (OVF) can be made. Beyond that, a "gold" radiographic standard to distinguish osteoporotic from non-osteoporotic VFs does not exist. Fracture-shaped vertebral deformity (FSVD) is defined as a deformity radiographically indistinguishable from vertebral fracture according to the best of the reading radiologist's knowledge. FSVD is not uncommon among young populations with normal bone strength. FSVD among an older population is called osteoporotic-like vertebral fracture (OLVF) when the FSVD is likely to be associated with compromised bone strength. In more severe grade deformities or when a vertebra is collapsed, OVF diagnosis can be made with a relatively high degree of certainty by experienced readers. In "milder" cases, OVF is often diagnosed based on a high probability rather than an absolute diagnosis. After excluding known mimickers, singular vertebral wedging in older women is statistically most likely an OLVF. For older women, three non-adjacent minimal grade OLVF (< 20% height loss), one minimal grade OLVF and one mild OLVF (20-25% height loss), or one OLVF with ≥ 25% height loss, meet the diagnosis of osteoporosis. For older men, a single OLVF with < 40% height loss may be insufficient to suggest the subject is osteoporotic. Common OLVF differential diagnoses include X-ray projection artifacts and scoliosis, acquired and developmental short vertebrae, osteoarthritic wedging, oncological deformities, deformity due to high-energy trauma VF, lateral hyperosteogeny of a vertebral body, Cupid's bow, and expansive endplate, among others.

Bone Marrow Adipose Tissue Is Increased in Postmenopausal Women With Postsurgical Hypoparathyroidism.

CONTEXT: Suppression of bone turnover, greater trabecular volume, and normal-high normal all-site bone mineral density (BMD) are hallmarks of postsurgical hypoparathyroidism (HypoPT). Impairment in the trabecular microarchitecture with possible higher risk of vertebral fractures (VF) in women with postmenopausal HypoPT has also been described. Currently, no data on bone marrow adipose tissue (BMAT) are available in HypoPT. OBJECTIVE: To assess BMAT by magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (1H-MRS) in postmenopausal women with chronic postsurgical HypoPT. METHODS: This cross-sectional pilot study, conducted at an ambulatory referral center, included 29 postmenopausal women (mean age 66 ± 8.4 years) with postsurgical HypoPT and 31 healthy postmenopausal women (mean age 63 ± 8.5). Lumbar spine MRI was performed and BMAT was measured by applying PRESS sequences on the L3 body. Lumbar spine, femoral neck, and total hip BMD were measured by dual x-ray absorptiometry (DXA); site-matched spine trabecular bone score (TBS) was calculated by TBS iNsight (Medimaps, Switzerland); VF assessment was performed with lateral thoracic and lumbar spine DXA. RESULTS: Fat content (FC) and saturation level (SL%) were higher (P <.0001 and P <.001), while water content (W) was lower in HypoPT compared to controls (P <.0001). FC significantly correlated with years since menopause and body weight (P <.05) in HypoPT, while TBS negatively correlated with FC and SL% (P <.05) and positively with residual lipids (RL) and W (P <.05). CONCLUSION: We demonstrate for the first time that BMAT is increased in postmenopausal women with postsurgical hypoparathyroidism and negatively associated with trabecular microarchitecture.

A software program for automated compressive vertebral fracture detection on elderly women's lateral chest radiograph: Ofeye 1.0.

Background: Because osteoporotic vertebral fracture (OVF) on chest radiographs is commonly missed in radiological reports, we aimed to develop a software program which offers automated detection of compressive vertebral fracture (CVF) on lateral chest radiographs, and which emphasizes CVF detection specificity with a low false positivity rate. Methods: For model training, we retrieved 3,991 spine radiograph cases and 1,979 chest radiograph cases from 16 sources, with among them in total 1,404 cases had OVF. For model testing, we retrieved 542 chest radiograph cases and 162 spine radiograph cases from four independent clinics, with among them 215 cases had OVF. All cases were female subjects, and except for 31 training data cases which were spine trauma cases, all the remaining cases were post-menopausal women. Image data included DICOM (Digital Imaging and Communications in Medicine) format, hard film scanned PNG (Portable Network Graphics) format, DICOM exported PNG format, and PACS (Picture Archiving and Communication System) downloaded resolution reduced DICOM format. OVF classification included: minimal and mild grades with <20% or ≥20-25% vertebral height loss respectively, moderate grade with ≥25-40% vertebral height loss, severe grade with ≥40%-2/3 vertebral height loss, and collapsed grade with ≥2/3 vertebral height loss. The CVF detection base model was mainly composed of convolution layers that include convolution kernels of different sizes, pooling layers, up-sampling layers, feature merging layers, and residual modules. When the model loss function could not be further decreased with additional training, the model was considered to be optimal and termed 'base-model 1.0'. A user-friendly interface was also developed, with the synthesized software termed 'Ofeye 1.0'. Results: Counting cases and with minimal and mild OVFs included, base-model 1.0 demonstrated a specificity of 97.1%, a sensitivity of 86%, and an accuracy of 93.9% for the 704 testing cases. In total, 33 OVFs in 30 cases had a false negative reading, which constituted a false negative rate of 14.0% (30/215) by counting all OVF cases. Eighteen OVFs in 15 cases had OVFs of ≥ moderate grades missed, which constituted a false negative rate of 7.0% (15/215, i.e., sensitivity 93%) if only counting cases with ≥ moderate grade OVFs missed. False positive reading was recorded in 13 vertebrae in 13 cases (one vertebra in each case), which constituted a false positivity rate of 2.7% (13/489). These vertebrae with false positivity labeling could be readily differentiated from a true OVF by a human reader. The software Ofeye 1.0 allows 'batch processing', for example, 100 radiographs can be processed in a single operation. This software can be integrated into hospital PACS, or installed in a standalone personal computer. Conclusions: A user-friendly software program was developed for CVF detection on elderly women's lateral chest radiographs. It has an overall low false positivity rate, and for moderate and severe CVFs an acceptably low false negativity rate. The integration of this software into radiological practice is expected to improve osteoporosis management for elderly women.

Osteomalacia and Vitamin D Status: A Clinical Update 2020.

Historically, rickets and osteomalacia have been synonymous with vitamin D deficiency dating back to the 17th century. The term osteomalacia, which literally means soft bone, was traditionally applied to characteristic radiologically or histologically documented skeletal disease and not just to clinical or biochemical abnormalities. Osteomalacia results from impaired mineralization of bone that can manifest in several types, which differ from one another by the relationships of osteoid (ie, unmineralized bone matrix) thickness both with osteoid surface and mineral apposition rate. Osteomalacia related to vitamin D deficiency evolves in three stages. The initial stage is characterized by normal serum levels of calcium and phosphate and elevated alkaline phosphatase, PTH, and 1,25-dihydroxyvitamin D [1,25(OH)2D]-the latter a consequence of increased PTH. In the second stage, serum calcium and often phosphate levels usually decline, and both serum PTH and alkaline phosphatase values increase further. However, serum 1,25(OH)2D returns to normal or low values depending on the concentration of its substrate, 25-hydroxyvitamin D (25OHD; the best available index of vitamin D nutrition) and the degree of PTH elevation. In the final stage, hypocalcemia and hypophosphatemia are invariably low with further exacerbation of secondary hyperparathyroidism. The exact,or even an approximate, prevalence of osteomalacia caused by vitamin D deficiency is difficult to estimate, most likely it is underrecognized or misdiagnosed as osteoporosis. Signs and symptoms include diffuse bone, muscle weakness, and characteristic fracture pattern, often referred to as pseudofractures, involving ribs, scapulae, pubic rami, proximal femurs, and codfish-type vertebrae. The goal of therapy of vitamin D-deficiency osteomalacia is to alleviate symptoms, promote fracture healing, restore bone strength, and improve quality of life while correcting biochemical abnormalities. There is a need for better understanding of the epidemiology of osteomalacia. Simplified tools validated by concurrent bone histology should be developed to help clinicians promptly diagnose osteomalacia. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

Imaging technologies in the differential diagnosis and follow-up of brown tumor in primary hyperparathyroidism: Case report and review of the literature.

Brown tumors are osteolytic lesions associated with hyperparathyroidism (HPT). They may involve various skeletal segments, but rarely the cranio-facial bones. We report a case of a young boy with a swelling of the jaw secondary to a brown tumor presenting as the first manifestation of primary HPT (PHPT). He was found to have brown tumor located in the skull, as well. Different imaging technologies were employed for the diagnosis and follow-up after parathyroidectomy. We enclose a review of the literature on the employment of such imaging technologies in the differential diagnosis of osteolytic lesions. A multidisciplinary approach comprising clinical, laboratory and imaging findings is essential for the differential diagnosis of brown tumor in PHPT.

How to define an osteoporotic vertebral fracture?

A vertebral deformity (VD) is not always a vertebral fracture (VF). Because of lack of a completely satisfactory "gold standard", there is no consensus on the exact definition of a VF. Therefore, it may sometimes be difficult, especially in mild cases, to discriminate the prevalent VF from a non-fracture deformity or short vertebral height (SVH). A combined standardized approach based on qualitative and semiquantitative (SQ) vertebral assessment may be the most option to correctly identify a VD as a VF. However this visual approach for VF identification is subjective, therefore it is mandatory an adequate training and experience of radiologist to reach a good sensitivity and specificity. Vertebral morphometry, objective and reproducible method, could be used only to evaluate the severity of VFs but requires the availability of reference values of vertebral height ratios. There is actually an evidentiary basis for suggesting that a qualitative approach by expert radiologists to morphological vertebral assessment, combined SQ and morphometric methods seem to be the preferred option for the correct diagnosis of VF as endplate or/and cortex fracture (ECF) or severe vertebral height loss.

Diagnostic accuracy of 3T magnetic resonance imaging in the preoperative localisation of parathyroid adenomas: comparison with ultrasound and 99mTc-sestamibi scans.

OBJECTIVES: To evaluate the diagnostic performance of 3TMRI in comparison with ultrasound (US) and 99mTc-sestamibi scan for presurgical localisation of parathyroid adenomas (PTAs) in patients with primary hyperparathyroidism (PHPT). METHODS: Fifty-seven patients affected by PHPT were prospectively enrolled and underwent US, 99mTc-sestamibi and 3TMRI. T2-weighted and post-contrast T1-weighted Iterative decomposition of water and fat with Echo Asymmetry and Least squares estimation (IDEAL) sequences were acquired. Diagnostic performance of US, 99mTc-sestamibi and MRI in localising PTAs to correct quadrant were compared according to surgical and pathological findings. RESULTS: According to surgical findings, US correctly localised 41/46 PTAs (sensitivity of 89.1%; specificity 97.5%; PPV 93.1% and NPV 95.6%); 99mTc-sestamibi correctly localised 38/46 PTAs (sensitivity 83.6%, specificity 98.3%, PPV 95% and NPV 93.7%). US and 99mTc-sestamibi combined had a sensitivity of 93.4% (43/46 PTAs), specificity of 98.3%, PPV 95% and NPV 98.3%. MRI correctly localised 45/46 PTAs (sensitivity 97.8%; specificity 97.5%; PPV 93.7% and NPV 99.2%). MRI was able to detect six adenomas missed by 99mTc-sestamibi and two adenomas missed by US. MRI and US were able to detect all enlarged parathyroid glands in patients with multiglandular disease. MRI identified six of seven ectopic adenomas. CONCLUSIONS: Our study demonstrated high diagnostic performance of 3T MRI in the preoperative PTAs quadrant localisation, as well as in patients with multiglandular disease and ectopic PTAs. MRI may be preferred to adequately select patient candidates for minimally invasive parathyroidectomy (MIP). KEY POINTS: • PTA(s) quadrant localisation by 3TMRI was more accurate than US+99mTc-sestamibi. • MRI identified all enlarged glands in multiglandular disease similarly to US. • MRI identified 6/7 ectopic PTAs similarly to 99mTc-sestamibi. • Presurgical PTA(s) localisation by 3TMRI select the optimal candidates for MIP.

Mineral metabolism abnormalities in patients with prostate cancer: a systematic case controlled study.

PURPOSE: Prostate cancer is the most common tumor in men. To the best of our knowledge a systematic assessment of bone and mineral abnormalities has not been performed in prostatic cancer patients consecutively enrolled. METHODS: This study was therefore carried out to investigate changes of skeletal and mineral metabolism in patients with prostate cancer (n = 69). A population of patients with cancer of various origin was also investigated as a control group (n = 53), since a comparison with non-prostate cancer patients has not been previously reported. RESULTS: In the prostatic cancer group, one patient had extremely high values of C-terminal Fibroblast Growth Factor 23, low values of tubular reabsorption of phosphate and very high values of bone alkaline phosphatase, suggesting the diagnosis of oncogenic osteomalacia. We found nine patients with primary hyperparathyroidism in the group of prostate cancer vs. only one in cancer patients group (p < 0.026). We stratified the population on the basis of Gleason score, prostate specific antigen and hormonal therapy. Using a generalized linear model with a logit link to predict the probability of developing primary hyperparathyroidism, only Gleason score, C-terminal fibroblast growth factor 23 and hormonal therapy had a significant effect (p < 0.05). Controlling for other covariates, a rise in fibroblast growth factor 23 increases the odds of developing primary hyperparathyroidism by 2% (p = 0.017), while patients with higher values of Gleason score have a much greater probability of developing primary hyperparathyroidism (log-odds = 3.6, p < 0.01). The probability decreases with higher values of Gleason score while on hormonal therapy; a further decrease was observed in patients on hormonal treatment and lower values of GS. Finally, lower grade of Gleason score without hormonal therapy have a significant protective factor (p < 0.01) decreasing the odds of developing primary hyperparathyroidism by 8%. CONCLUSION: We showed a remarkable prevalence of primary hyperparathyroidism in men with prostate cancer; the multivariate analysis demonstrates that higher aggressiveness of prostate cancer, as determined by Gleason score, is a significant predictor of increased risk of developing primary hyperparathyroidism.

Multiparametric ultrasonography and ultrasound elastography in the differentiation of parathyroid lesions from ectopic thyroid lesions or lymphadenopathies.

To evaluate the accuracy of ultrasound elastography with ElastoscanTM Core Index in the differential diagnosis of parathyroid lesions from ectopic thyroid nodules and lymph nodes. Seventy nine patients with repeatedly high levels of circulating intact parathyroid hormone, normal vitamin D and renal function tests, with an ultrasound scan showing a neck lesion, sharply demarcated from the thyroid lobules, were consecutively enrolled. Ultrasound with and without Color Doppler and ultrasound elastography were performed before histological examination. All ultrasound features, vascularization and ultrasound elastography diagnostic performance were assessed using ROC curves. Histological examination confirmed 47 parathyroid lesions, 18 thyroid ectopic nodules and 14 reactive lymph nodes. In distinguishing parathyroid from thyroid nodules, shape had a 100 % sensitivity (95 % CI 92.4-100) and 50 % specificity (95 % CI 37.2-64.7), cleavage had a 85.1 % sensitivity (95 % CI 72.3-92.6) and 77.8 % specificity (95 % CI 65.1-88) while peripheral vascularization had a sensitivity of 91.5 (95 % CI 79.6-97.6) and specificity of 72.2 (95 % CI 46.5-90.3). An ElastoscanTM Core Indexof 1.28 was 46 % sensitive (95 % CI 33.4-58.7) and 77 % specific (95 % CI 66.2-89.1) in discriminating parathyroid lesions from thyroid nodules. An ElastoscanTM Core Index of 1.0 was 78 % sensitive (95 % CI 65.1-88) and 71 % specific (95 % CI 56-81.3) in discriminating parathyroid lesions from lymph nodes (p = 0.045). An ElastoscanTM Core Index greater than 2.58 had a 100 % sensitivity (95 % CI 43.8-100) and 95.4 % specificity (95 % CI 38.3-99.7) in discriminating malignant from benign parathyroid nodules. ElastoscanTM Core Index was significantly higher in thyroid nodules than in reactive lymph nodes (1.18 ± 0.62, p = 0.008). The ultrasound features of cleavage and peripheral vascularization help to differentiate parathyroid from thyroid nodules. ElastoscanTM Core Index can improve ultrasound discrimination of parathyroid lesions from lymph nodes. The ElastoscanTM Core Index is significantly higher in malignant than in benign parathyroid lesions.

Decompression versus decompression and fusion for degenerative lumbar stenosis: analysis of the factors influencing the outcome of back pain and disability.

BACKGROUND: The objective of this study is to evaluate the factors influencing the outcome of back pain and disability in patients operated for lumbar stenosis without instability and deformity using two classical surgical techniques: decompression alone and decompression plus fusion. METHODS: This is a retrospective cohort study of patients who underwent lumbar surgery with standard posterior decompression or standard posterior decompression plus pedicle screw fixation for degenerative lumbar stenosis without deformity, spondylolisthesis or instability at our department from June 2010 to January 2014. They were divided into two groups: decompression group (D) and decompression-fusion group (F). We analyzed the following factors: age, gender, levels of stenosis, pre-surgical "micro-instability", and post-surgical "micro-instability". RESULTS: A total of 174 patients were enrolled in the study. Both Graphic Rating Scale (GRS) and Oswestry Disability Index (ODI) scores were significantly decreased after surgery (P<0.001). Female patients appeared to have lesser improvements from surgery, for both D and F groups. An analysis of variance using the decrease of pain (GRS pre-post) as dependent variable and type of surgery, age, gender and their interaction as factors showed that the main effects of type of surgery and gender were significant. The analysis of variance for the decrease of pain (GRS) and disability (ODI) according to the levels of stenosis showed a significant interaction for GRS scores. Female patients that underwent fixation surgery reported the least improvement in disability. A significant interaction was found on the one-way analysis of variance for the D group without pre-surgical micro-instability using post-surgical micro-instability as factor. CONCLUSIONS: Our study supports posterior decompression alone as the gold standard option as treatment for lumbar stenosis without instability and deformity. Additional fusion should be considered only to prevent post-surgical instability. The "micro-instability" is a radiological finding that has its clinical surrogate but is not able to guide the choice of the type of surgery. Moreover the significance of "micro-instability" is still unclear. We suggest a prospective study following patients with asymptomatic micro-instability to definitively understand the clinical history.

High prevalence of abdominal aortic calcification in patients with primary hyperparathyroidism as evaluated by Kauppila score.

OBJECTIVE: The prevalence of abdominal aortic calcification (AAC) in primary hyperparathyroidism (PHPT) is unknown. We assessed both prevalence and severity of AAC in PHPT postmenopausal women. METHODS: In this study 70 PHPT postmenopausal women and 70 age- and sex-matched controls were enrolled. Each participant underwent biochemical evaluation, lateral spine radiograph, bone mineral density (BMD) measurement (lumbar, femoral, radial sites), and kidney ultrasound. Lateral lumbar films were analyzed in the region of L1-L4 vertebrae and the Kauppila score (a semi-quantitative grading system) was used to assess the severity of AAC. RESULTS: There were no differences regarding demographic and cardiovascular risk factors in the two groups. PHPT patients had higher prevalence of kidney stones (30% vs 7%, P=0.0008) and lower radial BMD values (0.558±0.071 vs 0.588±0.082 g/cm(2), P<0.05) compared with controls. PHPT patients showed higher prevalence of AAC (31 vs 18, P=0.03), with more severe calcifications (Kauppila score 7.35±6.1 vs 5.05±3.5, P=0.007). PHPT patients with AAC were older and had been suffering from the disease for a longer period compared with those without ACC. Moreover, PHPT patients with severe AAC had mean higher serum parathyroid hormone levels compared with patients with moderate or mild calcifications. In PHPT patients with AAC, multiple regression analysis, adjusted for age and years since diagnosis, showed that only parathyroid hormone significantly correlated with Kauppila score. CONCLUSION: We found a higher prevalence and severity of AAC in PHPT related to parathyroid hormone effect.

Imaging of the parathyroid glands in primary hyperparathyroidism.

Primary hyperparathyroidism (PHPT) is one of the most frequent endocrine diseases worldwide. Surgery is the only potentially curable option for patients with this disorder, even though in asymptomatic patients 50 years of age or older without end organ complications, a conservative treatment may be a possible alternative. Bilateral neck exploration under general anaesthesia has been the standard for the definitive treatment. However, significant improvements in preoperative imaging, together with the implementation of rapid parathyroid hormone determination, have determined an increased implementation of focused, minimally invasive surgical approach. Surgeons prefer to have a localization study before an operation (both in the classical scenario and in the minimally invasive procedure). They are not satisfied by having been referred a patient with just a biochemical diagnosis of PHPT. Imaging studies must not be utilized to make the diagnosis of PHPT. They should be obtained to both assist in determining disease etiology and to guide operative procedures together with the nuclear medicine doctor and, most importantly, with the surgeon. On the contrary, apart from minimally invasive procedures in which localization procedures are an obligate choice, some surgeons believe that literature on parathyroidectomy over the past two decades reveals a bias towards localization. Therefore, surgical expertise is more important than the search for abnormal parathyroid glands.

MR appearance of parathyroid adenomas at 3 T in patients with primary hyperparathyroidism: what radiologists need to know for pre-operative localization.

OBJECTIVES: To identify frequent MRI features of parathyroid adenomas (PTAs) in patients with primary hyperparathyroidism (PHPT) using a fast protocol with a 3 T magnet. METHODS: Thirty-eight patients with PHPT underwent a 3 T-MR. All patients had positive US and Tc-99 sestamibi, for a total number of 46 PTAs. T2-weighted IDEAL-FSE and T1 IDEAL-sequences, before and after contrast, were performed. Five features of PTAs were recognised: hyperintensity, homogeneous or "marbled" appearance and elongated morphology on T2-sequences; cleavage plane from thyroid gland on T2-outphase; rapid enhancement in post-contrast T1. Image quality for T2-weighted IDEAL FSE and usefulness for IDEAL post-contrast T1-weighted and T2-outphase sequences were also graded. RESULTS: PTAs were hyperintense in T2-sequences in 44/46 (95.7%), "marbled" in 30/46 (65.2%) and elongated in 38/46 (82.6%) patients. Cleavage plane was observed in 36/46 (78.3%), and rapid enhancement in 20/46 (43.5%) patients. T2-sequences showed both excellent fat suppression and image quality (average scores of 3.2 and 3.1). T2-outphase images demonstrated to be quite useful (score 2.8), whereas, post-contrast T1 images showed a lower degree of utility (score 2.4). CONCLUSIONS: A fast protocol with 3.0-T MRI, recognising most common features of PTAs, may be used as a second-line method in the preoperative detection of PTAs. KEY POINTS: 3 T MRI protocol based on T2-weighted IDEAL FSE sequences was used. T2-hyperintensity and elongated morphology are common features of PTAs. 3 T MRI could be used in the preoperative detection of PTAs.

Six-year follow-up of a characteristic osteolytic lesion in a patient with tumor-induced osteomalacia.

OBJECTIVE: Tumor-induced osteomalacia is a rare paraneoplastic syndrome characterized by hypophosphatemia and inappropriately normal or low 1,25-dihydroxyvitamin D. CLINICAL CASE: Here, we report a 6-year postoperative follow-up of a patient with oncogenic osteomalacia with a distinctive skeletal manifestation. The latter was characterized by an almost linear lytic lesion of a few millimeters with irregular borders, mainly involving the trabecular compartment but extending into cortical shell, located in the middle third of the right fibula. Six years after tumor resection, a sclerotic repair with a complete recovery was observed. Furthermore, we monitored a striking increase in bone mineral density throughout the observation period, reaching a peak of 73% over basal values at lumbar spine after 2 years; at total femur and radius, the peak was 47.5 and 4.6% respectively, after 4 years from tumor resection. CONCLUSIONS: We report for the first time that an osteolytic lesion may be part of the skeletal involvement in tumor-induced osteomalacia.

Morphometric vertebral fractures in postmenopausal women with primary hyperparathyroidism.

CONTEXT: An increased risk of fracture in patients with primary hyperparathyroidism (PHPT) compared to the general population has been reported, but available data are controversial. OBJECTIVE: The aim of the study was to evaluate the rate of vertebral fractures (VFs) by dual-energy x-ray absorptiometry in postmenopausal women with sporadic PHPT and compare the results with a control group. DESIGN AND SETTING: A case-control study was performed at a referral center. PARTICIPANTS: A total of 150 consecutive patients and 300 healthy women matched for age and menopausal age participated in the study. RESULTS: VFs were detected in 37 of 150 (24.6%) patients and 12 of 300 (4.0%) controls (P < 0.0001). The majority of VFs were mild. Stepwise multiple logistic regression analysis showed that in PHPT patients lumbar spine bone mineral density was the only variable independently associated with the prevalence of VFs (P = 0.003). The rate of fracture was higher in symptomatic (34.1%) than asymptomatic (21.1%) patients, but this difference was not statistically significant (P = 0.15). Among asymptomatic patients, fracture rate was significantly higher in those who met the criteria for parathyroidectomy (28.1%) than in those who did not (11.1%) (P = 0.03). Compared to controls, the fracture rate was significantly higher in patients with symptomatic and asymptomatic PHPT who met the criteria for surgery (P < 0.0001), but not in those who did not meet the criteria (P = 0.06). CONCLUSIONS: VF rate is increased in postmenopausal women with PHPT compared to controls, independently of whether they are classified as symptomatic or asymptomatic. The question of whether the finding of mild morphometric VFs in the latter represents an indication for parathyroid surgery remains to be established.

Lumbar bone mineral density as the major factor determining increased prevalence of vertebral fractures in monoclonal gammopathy of undetermined significance.

The possible relationships between biochemical measurements and both densitometric and radiographic indexes of skeletal fragility were evaluated in 65 postmenopausal women with monoclonal gammopathy of undetermined significance (MGUS). There was a significantly higher prevalence of vertebral fractures in the MGUS group compared with a control population (P < or = 0.001). The MGUS patients were then grouped according to the presence or absence of at least one mild vertebral fracture. Patients with fractures (Fx, n=34) were older (62.8 +/- 6.1 years), with long-standing disease (8.8 +/- 7.1 years) when compared with those without fractures (NFx, n=31; 59.7 +/- 5.0 years, P < or = 0.05 and 5.8 +/- 4.1 years, P < or = 0.05). The receptor activator of nuclear factor kappa-B ligand/osteoprotegerin ratio was higher in Fx compared with NFx (0.092 +/- 0.018 vs. 0.082 +/- 0.020; P < or = 0.05). Lumbar spine (0.811 +/- 0.14 vs. 0.956 +/- 0.12 g/cm2), femoral neck (0.660 +/- 0.09 vs. 0.747 +/- 0.10 g/cm2) and total bone mineral density (BMD) (0.788 +/- 0.11 vs. 0.884 +/- 0.11 g/cm2) were lower (all P < or = 0.001) in FxMGUS compared with Nfx patients. Receiver operating characteristic curves identified lumbar BMD as the variable that best predicted vertebral fractures (area under the curve 0.817; 95% confidence interval, 0.713-0.921). This study provides an indication for the measurement of BMD in MGUS patients, as a means of predicting vertebral fractures, especially in those that are asymptomatic. Patients with prevalent fractures should undergo pharmacological treatment to prevent further fractures.

[Bone mass, bone metabolism, and prevalence of spinal fractures in recipients of allogenic bone marrow transplantation for leukemia]. / Massa ossea, metabolismo scheletrico e prevalenza delle fratture vertebrali in pazienti precedentemente sottoposti a trapianto di midollo osseo allogenico per leucemia.

The aim of this study was to evaluate in 65 patients, who had previously undergone allogenic bone marrow transplantation (ABMT), the bone mineral density (BMD), the skeletal turnover and the prevalence of vertebral fractures. At the moment of recruiting, 10 of 65 transplanted subjects (15.3%) presented with signs of rejection of the transplanted tissue, thus they were excluded. The remaining 55 patients (21 males, 34 females, mean age 30.8 +/- 6.4 years), with a follow-up of 60 +/- 9 months after the transplant and without any treatment inducing osteopenia, underwent ABMT respectively for: chronic myeloid leukemia (n = 24); acute myeloid leukemia (n = 18); acute lymphatic leukemia (n = 13). One hundred and ten healthy control subjects (42 males and 68 females, mean age 31.0 +/- 3.7 years) matching with the patients for age, weight and height, were successively enrolled. All the participants were submitted to a densitometric evaluation (DEXA) of lumbar spine (L1-L4), of femoral neck and total femur; besides some skeletal metabolism parameters were dosed, such as: total alkaline phosphatase, bone alkaline phosphatase and urinary excretion of C-terminal telopeptide fragments normalized to creatinine. On the contrary, the morphometric evaluation, performed through a lateral dorsolumbar radiography, was actually carried out only in patients who had already undergone ABMT. The L1-L4 BMD study showed: 10/55 osteoporotic (18.1%), 19/55 osteopenic (34.5%) and 26/55 normal patients (47.4%). In transplanted patients BMD values, obtained at the three considered sites, resulted significantly reduced (p < 0.01) in comparison to controls. Moreover, in patients who underwent ABMT, a statistically significant increase was observed, in comparison to healthy subjects, in total alkaline phosphatase (p < 0.01), in bone alkaline phosphatase (p < 0.01) and in urinary excretion of C-terminal telopeptide fragments normalized to creatinine levels (p < 0.001). Seven of the 55 transplanted patients (12.7%) presented at the moment of Rx morphometric evaluation at least one vertebral fracture: 6 of whom were affected by osteoporosis and 1 by osteopenia. In conclusion, the subjects who had previously undergone ABMT maintain, even at a certain time after the transplant and without any rejection, an increased skeletal turnover and BMD values meanly lower than normal, leading to an increased risk for vertebral fracture.

[Turnover of bone metabolism and prevalence of vertebral fractures in adrenal incidentalomas]. / Valutazione del turnover osseo e delle fratture vertebrali in incidentalomi surrenalici.

Aim of the study was to evaluate, in a homogeneous group of patients with adrenal incidentalomas (AI), calcium-phosphorus metabolism alterations, bone mineral density (BMD) and the prevalence of vertebral fractures. We selected 46 patients with adrenal incidentalomas (26M, 20F; age: M = 61 +/- 14, F = 65 +/- 10 years, BMI: M = 26.2 +/- 4 Kg/m2, F = 28.8 +/- 4 Kg/m2) compared with 84 normal subjects (NS) (44M, 40F; age: M = 60 +/- 10, F = 62 +/- 8 years; BMI: M = 27 +/- 2 Kg/m2, F = 28.1 +/- 4.5 Kg/m2). In all subjects we estimated calcium-phosphorus parameters. Our results showed that in 46 patients with AI there were a significant reduction of BMD-LS (0.915 +/- 0.176 g/cm2; p = 0.01) and of BMD-FN (0.710 +/- 0.129; p = 0.034) respect to those of NS (respectively: 0.994 +/- 0.14 9 g/cm2; 0.758 +/- 0.117 g/cm2). BMD-LS of the 20 women with AI (0.864 +/- 0.157 g/cm2, p = 0.01) was significantly reduced compared with the 40 female normal subjects (0.904 +/- 0.148 g/cm2); BMD-LS of the 26 men with AI (0.967 +/- 0.187 g/cm2; p = 0.048) was significantly reduced compared with the male normal subjects (1.048 +/- 0.133 r/cm2; p = 0.048). The MXA showed vertebral fractures in 15 (75%) of 20 patients with AI (2 patients were osteoporotic, 9 osteopenic and 4 normal at the MXA scans). In 20 women with AI, compared with female NS, we found a significant reduction of serum 25 OH D3 (p = 0.024) levels and a significant increase of plasma i-PTH (P = 0.04) value; and we found a negative correlation between plasma i-PTH and 25 OH D3 values (r = -0.451; p > 0.045). In conclusion, we demonstrated that patients with non-functioning adrenal incidentalomas present calcium-phosphorus metabolism alterations, associated at a reduction of BMD and an increase of vertebral fractures.