Daniele Diacinti

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.

Effects of salmon calcitonin on the bone loss induced by ovariectomy

SummaryWe present the results of a 12-month clinical study assessing the effects of synthetic salmon calcitonin (sCT) on a group of fertile white women who had undergone ovariectomy for uterine fibromatosis. The study was performed to verify whether CT can prevent the loss of bone mass and the changes in calcium-phosphorus metabolism associated with acute estrogen deficiency. The study consisted of an initial double-blind phase of 6 months, followed by a 6-month open period. Treated patients were given 100 MRC U of synthetic salmon CT injected i.m. in the morning, every other day, starting on the 7th day after the operation and continued for 12 months. Control patients received a placebo injection for the first 6 months; subsequently, they too were treated with sCT i.m. every other day for 6 months at the same dose as the 12 month-treated group. All patients received 500 mg of elementary calcium p.o., b.i.d. Bone mineral content (BMC) was measured at the extreme distal radius of the nondominant arm by a dual photon bone densitometer which utilizes two radio nuclides, 241 Am and 125 I, with energies of about 60 and 30 KeV. Biochemical parameters of the calcium-phosphorus metabolism were also measured. After 12 months of study, no significant changes of BMC were observed in the 12 months sCT treated group, while control patients, treated 6 months after the ovariectomy, showed a significant decrease in BMC values. Total hydroxyproline/ creatinine (OHPr/Cr) ratio, which increased after ovariectomy, returned to normal after the first month of sCT administration in the continuously treated group whereas it remained high in the control group up to the 6th month of observation, declining thereafter in coincidence with sCT treatment. The behavior of Bone GLA-protein (BGP), like that of the nondializable OHPr/Cr ratio, was substantially similar in both treated and control groups for the entire period of observation. These results show that prophylactic administration of salmon CT in ovariectomized women prevent estrogen deficiency-induced bone loss, inhibiting skeletal resorption and allowing osteogenesis to occur normally.

Prevalence of Kidney Stones and Vertebral Fractures in Primary Hyperparathyroidism Using Imaging Technology

CONTEXT The fourth International Workshop on the Management of Asymptomatic Primary Hyperparathyroidism (PHPT) has recently suggested that skeletal and renal imaging be routinely conducted. So far, no study has systematically assessed this issue. OBJECTIVE The objective was to evaluate the prevalence of kidney stones (KS) and vertebral fractures (VFs) in a cohort of patients with PHPT utilizing noninvasive imaging technology. DESIGN This was a prospective study evaluating patients consecutively diagnosed with PHPT in a single center over a 5-year period (2009-2013). SETTING The setting was a referral center. PATIENTS There were a total of 140 patients with PHPT (127 women [18 premenopausal and 109 postmenopausal] and 13 men; mean age, 63.2 ± 11 y). MAIN OUTCOMES MEASURES Main outcome measures were the prevalence of KS by abdominal ultrasound, osteoporosis by dual-energy x-ray absorptiometry (DXA) (lumbar spine, femoral neck, total hip, and distal 1/3 radius), and VFs by vertebral spine x-ray, with attention to those categorized as symptomatic or asymptomatic. RESULTS Fifty-five percent of all subjects had KS by ultrasound, 62.9% had osteoporosis by T-score at any site, and 35.1% had VFs by x-ray. There was no difference in the incidence of VFs and densitometric osteoporosis between symptomatic and asymptomatic patients (VFs, 34.4 vs 34.7%; osteoporosis by DXA, 59.4 vs 65.8%), whereas more KS were detected in symptomatic (78%) than asymptomatic (35.5%). Twenty-two percent of patients classified as asymptomatic at baseline without osteoporosis by DXA were found to have KS and/or VFs. CONCLUSIONS Nephrolithiasis and VFs are common in asymptomatic subjects with PHPT. The results provide evidence in support of recent recommendations that a more proactive approach be taken to detect silent bone and stone disease in asymptomatic PHPT.

The combination of FRAX and Ageing Male Symptoms scale better identifies treated HIV males at risk for major fracture.

Osteoporosis and hypogonadism are common in men with HIV infection. Ageing Male Symptoms (AMS) scale measures symptoms related to hypogonadism. FRAX provides 10‐year probability of major fractures. We investigated the role of AMS scale combined with FRAX without bone mineral density (BMD), in identifying HIV men with bone fragility.

Secondary Osteoporosis in Men and Women: Clinical Challenge of an Unresolved Issue

Objective. To evaluate the clinical and etiological factors of osteoporosis. We also tested the FRAX algorithm to compare the assessment of fracture risk in patients with primary or secondary osteoporosis. Methods. A prospective study carried out in a large sample of 123 men and 246 women. All subjects had a biochemical, densitometric, and radiological examination of thoracic and lumbar spine. Results. The prevalence of primary (men 52.9% vs women 50%; p = nonsignificant) and secondary (men 21.1% vs women 17.5%; p = nonsignificant) osteoporosis did not differ between the sexes. In contrast, the prevalence of primary osteoporosis was significantly higher than secondary causes (p < 0.0001) in both men and women. While women came to our attention for prevention of osteoporosis, men sought help because of clinical symptoms or disease-related complications, such as fractures. As evaluated by the FRAX tool, patients with osteopenia do not need treatment, in agreement with Italian guidelines. The estimated risk of major osteoporotic and hip fractures was significantly higher in women with secondary osteoporosis compared to men and also compared to women with primary osteoporosis. Conclusion. The prevalence of secondary osteoporosis in men is similar to that in women and it is less frequent than commonly reported. In patients with secondary osteoporosis, FRAX calculation may provide an estimate of a particularly high fracture risk in patients whose bone fragility is usually attributed to another disease.

Vertebral morphometry by X-ray absorptiometry: Which reference data for vertebral heights?

INTRODUCTION The recent improvement in the resolution of dual-energy X-ray absorptiometry (DXA) images enables most vertebral levels to be seen adequately and thus DXA may be a worthwhile alternative to radiologic morphometry for the identification of vertebral fractures (VF). In this multicenter study, we have derived reference data for vertebral heights and their ratios in Italian women using morphometric X-ray absorptiometry (MXA). METHODS DXA scans were acquired in 1254 consecutive pre- and postmenopausal women, (mean age 63.7 ± 11.3, range 26-88 yrs), referred to six osteoporosis centers. MXA analysis of these images was performed by the same operator measuring vertebral heights and height ratios from L4 to T4. We calculated measures of central tendency and dispersion of vertebral heights and vertebral ratios using different approaches (mean and standard deviation as well as median and interquartile range of raw data, mean and standard deviation of trimmed data using an iterative algorithm, and mean and standard deviation of not fractured vertebrae). RESULTS Independently of the approach that we used, all the measures of central tendency were similar, while significant differences were found when compared with reference ranges in other populations. The vertebral heights of our sample at every vertebral level were significantly smaller than both Rea population and the Lunar reference values, even after normalization. Splitting data according to age groups, there was a decrease in the vertebral heights and ratios between the younger and older women. CONCLUSIONS This study demonstrates that reference data for MXA should be population specific and age matched.

Effect of a single oral dose of 600,000 IU of cholecalciferol on muscle strength: A study in young women

Background: The effect of a single large oral dose of vitamin D on muscle function in young people with vitamin D deficiency has not been investigated so far. Aim: We evaluated the effect of a single oral dose of 600, 000 IU of cholecalciferol on muscle strength. Subjects and methods: Eighteen young women with vitamin D deficiency received a single oral dose of 600, 000 IU of cholecalciferol. We evaluated changes in maximal voluntary contraction (MVC) and speed of contraction (S) in response to cholecalciferol by using an hand held dynamometer at 3, 15, 30, 60 and 90 days, compared to baseline. Results: We observed no significant change in MVC and S values, a significant increase of 25-hydroxyvitamin D [25(OH)D] and 1, 25-dihydroxyvitamin D [1, 25(OH)2D] and a significant decrease in serum parathyroid hormone (PTH) (p<0.001 for all). A significant correlation was found between MVC and S and serum phosphorus (P) after supplementation (p<0.02 and p<0.05, respectively). Conversely, we observed no association between the parameters of muscle strength and 25(OH)D, ionized calcium (Ca2+), PTH and 1, 25(OH)2D. Conclusions: A single dose of 600, 000 IU of cholecalciferol does not directly enhance handgrip strength in young women with vitamin D deficiency. More studies are needed on the indirect effect of the hormone on muscle.

Effect of endogenous cholecystokinin on postprandial gallbladder refilling. Ultrasonographic study in healthy subjects and in gallstone patients.

The postprandial release of cholecystokinin (CCK) regulates gallbladder (GB) contraction but little is known about the role, if any, of the still-elevated CCK blood levels on subsequent GB refilling. To assess the role of CCK in GB refilling, a CCK-receptor antagonist, loxiglumide, or saline were infused intravenously in a random double-blind fashion after the ingestion of a liquid test meal in 16 healthy subjects. An identical study protocol was performed in 10 GB “contractor” patients with radiolucent stones to ascertain whether the reported reduced CCK effect on GB emptying also affects GB refilling. GB volumes were assessed ultrasonographically in the fasting state and for 150 min at 15-min intervals after meal ingestion. GB volumes during postprandial refilling were significantly greater during loxiglumide than placebo infusion (P<0.01), but they did not differ between gallstone and control subjects. In conclusion, postprandial endogenous CCK has a relevant role in delaying GB refilling, and this effect is not altered in patients with radiolucent gallstones.

Misdiagnosis of vertebral fractures on local radiographic readings of the multicentre POINT (Prevalence of Osteoporosis in INTernal medicine) study

BACKGROUND Osteoporotic vertebral fractures (VFs) are often misdiagnosed because asymptomatic and occurring in the absence of specific trauma. Further, diagnostic assessment of VFs may be suboptimal. AIM OF THE STUDY To assess the misdiagnosis of vertebral fractures on local radiographic readings in the cohort of patients enrolled in the POINT study. METHODS We enrolled hospitalised patients, admitted for any cause to the Internal Medicine Units of 37 hospitals participating to the cross-sectional previously published POINT study. The assessment of VFs was performed both by local radiologists and by two expert skeletal radiologists, by using semiquantitative method (SQ). To better evaluate mild vertebral deformities, the two central radiologists also used the algorithm-based qualitative assessment (ABQ). RESULTS The radiographs of 661 patients (401 females; mean age 75.8±8.0) were evaluated. The inter-reader percent agreement between two central expert radiologists per-vertebra assessment was excellent (99.78%; k=0.984; 95% CI, 0.977-0.991). Central reading identified 318/661 (48.1%) patients with at least one VF. Local and central readings agreed in 502/661 (75.9%) patients, resulting in a fair reproducibility (k=0.52; 95% confidence interval 0.44-0.59). Diagnostic performance parameters of local readings were: sensitivity 76.1%; specificity 75.8%; PPV 74.46%; NPV 77.38%). By examining 9254 vertebrae, central and local readers diagnosed 665 (7.2%) and 562 (6.1%) VFs respectively. Misdiagnosis (102 false positives and 205 false negatives) mainly occurred for mild VFs. Local readings identified correctly 460 out 665 VFs diagnosed by central readings, resulting in sensitivity of 69.2% and PPV of 81.8%. CONCLUSIONS Following a standardized protocol of acquisition techniques and of interpretation criteria, an excellent agreement between local and central readings for moderate and severe vertebral fractures resulted. However a significant amount of mild vertebral fractures, that are the most of VFs, were misdiagnosed by local radiologists. In order to improve VFs assessment, the radiologists should be trained and sensitized in relation to the relevant clinical significance of osteoporotic VFs identification.

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.