[Guidelines for the diagnosis, prevention and treatment of osteoporosis]. / Linee guida per la diagnosi, prevenzione e terapia dell'osteoporosi Società Italiana dell'Osteoporosi, del Metabolismo Minerale e delle Malattie dello Scheletro - SIOMMMS.

UNLABELLED: The guidelines for the osteoporosis management were first drafted by a working group and then critically evaluated by the board of SIOMMMS. The most relevant points are: DEFINITION: Osteoporosis is defined as a quantitative and qualitative deterioration of bone tissue leading to increased risk of fracture. Postmenopausal and senile osteoporosis are defined as primitive. DIAGNOSIS: The cornerstone for the diagnosis of osteoporosis is the measurement of bone mineral density (BMD) by DXA (dual-energy X-ray absortiometry) at the femoral neck with T-score values <-2.5, following the WHO definition. Other DXA sites or technologies for measuring bone mass are also acceptable when the former is not accessible. A BMD evaluation is recommended to all women above 65 years of age. At younger age or in man the bone assessment is recommended only in subjects with specific risk factors. A control of bone mass measurement is seldom required before 2 years. DIFFERENTIAL DIAGNOSIS: A few biochemical tests such as serum and urinary calcium, protein electrophoresis, serum creatinine and ESR are usually sufficient to exclude most secondary types of osteoporosis. The value of the so called bone turnover markers for the diagnosis and follow-up of osteoporosis remains uncertain. Several secondary forms of osteoporosis require a specific diagnostic and therapeutic management. PREVENTION: The osteoporosis prevention should be based on the elimination of specific risk factors such as inadequate calcium and vitamin D intake, smoking and sedentary life. The use of pharmacological agents in subjects with BMD values >-2.5 is usually not justified. Pharmacological intervention: The use of drugs registered for the treatment of osteoporosis are recommended when the benefits overcome the risk. This is the case only when the risk of fracture is rather high. FRAX is recognized as a useful tool for easily estimate the long-term fracture risk. SIOMMMS with these guidelines is committed to validate and further develop this diagnostic tool.

Relationship of volumetric bone mineral density and structural parameters with ERalpha gene polymorphisms.

Bone mineral density (BMD) contributes to bone strength, and methods for clinical assessment of bone quality characteristics beyond what can be gathered by BMD are awaited. Peripheral quantitative computed tomography (pQCT) allows for separate assessments of cortical and trabecular bone, providing information on bone geometry. Previous studies examining the relationship between estrogen receptor alpha (ERalpha) gene polymorphisms and BMD have been performed in large populations. However, only limited information is available on the possible segregation of ERalpha gene polymorphisms with bone structural properties. The aim of our study was to evaluate the association of XbaI and PvuII ERalpha gene polymorphisms with QCT parameters. We studied 900 subjects (541 women, 449 men) participating to the InCHIANTI study. By tibial pQCT we evaluated trabecular volumetric BMD, cortical volumetric BMD, cortical bone area, and cortical thickness (CtTh). Subjects were genotyped for ERalpha gene PvuII and XbaI polymorphisms. Analysis of variance was used for statistical analysis. Male subjects with PP and XX genotypes had higher geometric parameters, and female subjects with XX and PP genotypes showed higher densitometric parameters than other genotypes; however, the differences did not reach statistical significance. After adjustment for potential confounders, we found a significant (P = 0.002) CtTh difference across PvuII polymorphism in male subjects, with higher CtTh values in PP genotypes with respect to Pp and pp genotypes. These results show a relationship between the presence of the P allele and higher values of CtTh in male subjects, indicating for ERalpha a role in the control of tibial bone geometry.

FokI polymorphism of the vitamin D receptor gene correlates with parameters of bone mass and turnover in a female population of the Italian island of Lampedusa.

One of the most promising genetic approaches to dissecting a multifactorial disease is represented by genetically isolated population studies. We studied a genetic marker in a cohort of women living on the Mediterranean island of Lampedusa, a geographically isolated population. Lampedusa, located between the African coast and Sicily, consists of a young genetic isolate (<20 generations) with an exponential growth in the last generations. We analyzed the association between the FokI vitamin D receptor (VDR) gene polymorphism, previously proposed as a predictor of bone mass, with parameters of bone mass and turnover in a cohort of pre- and postmenopausal women living on Lampedusa. In 424 women (277 postmenopausal and 147 premenopausal), allelic frequencies were 49% for the F allele and 51% for the f allele. Using analysis of covariance, we found that subjects with ff genotype exhibited a significantly (P < 0.001) lower lumbar spine bone mass, by dual-energy X-ray absorptiometry, and lower values of bone ultrasonographic parameters (speed of sound and broadband ultrasound attenuation) relative to those with Ff and FF genotypes. Conversely, osteocalcin and serum cross-laps were significantly higher in ff and Ff compared to FF genotype. Our data suggest that FokI VDR polymorphism may contribute to the determination of bone mass and turnover in both pre- and postmenopausal women in this geographically isolated population.

Bone ultrasonography in glucocorticoid-induced osteoporosis.

Osteoporosis is one of the major complications of glucocorticoid (GC) therapy. Few data are available on the usefulness of quantitative ultrasound (QUS), a technique that could also theoretically provide information on bone structure, in the management of glucocorticoid-induced osteoporosis (GIO). This study aimed (1) to evaluate the ability of QUS in detecting bone impairment and in being associated with the prevalence of fragility fracture in GC patients; and (2) to assess whether QUS parameters, and particularly the graphic trace analysis of QUS signal at phalanges, show any peculiar pattern of GIO. We studied 192 patients (136 women and 56 men, mean age 56.7 +/- 14.2 years) on treatment with GCs for at least 6 months, and 192 sex- and age-matched controls. In all subjects, we measured bone mineral density (BMD) at lumbar spine and at femur by DXA, and ultrasound parameters at calcaneus and phalanges. All DXA and QUS parameters were significantly lower in GC patients than in controls and in fracture than in nonfracture GC patients. BMD at lumbar spine showed the best ability in discriminating GC patients with or without fractures. Among QUS parameters, stiffness showed a discriminatory ability significantly better than AD-SoS. BMD at lumbar spine and total femur, stiffness, and AD-SoS are able to predict the odds of fragility fracture event. QUS parameters of the postmenopausal GC patients (n = 105) and of the postmenopausal healthy controls (n = 101) were also compared with those obtained in a separate sample of 90 postmenopausal osteoporotic women (PMO). All parameters were significantly lower in GC patients and in PMO than in controls, without any significant difference between GC and PMO. Our findings show that QUS can be useful in the assessment of glucocorticoid-induced bone impairment. In addition, in this study we found no alteration in QUS parameters or in the graphic trace analysis which could differentiate between GIO and PMO. Further longitudinal studies are needed to define the role of QUS in the prediction of fracture risk and in the clinical management of GIO.

Feasibility of quantitative ultrasound measurements on the humerus of newborn infants for the assessment of the skeletal status.

Quantitative ultrasound (QUS), although widely used in adults has, so far, been scarcely employed in newborn infants and children. This study aimed to evaluate the feasibility of the use of QUS in newborn children and the factors influencing QUS parameters. In 140 consecutive healthy full-term newborn babies (76 male and 64 female; gestational age: 39.5 +/- 1.5 weeks) QUS parameters were assessed within 3 days of the child's birth at the distal diaphysis of the humerus by use of Bone Profiler, after an appropriate modification of caliper and software. In all subjects we evaluated the amplitude-dependent speed of sound (AD-SoS) (meters per second), the characterizing graphic trace parameters [signal dynamic (SDy), fast wave amplitude (FWA) and bone transmission time (BTT)], SoS (meters per second), that is, the speed of sound calculated on the first peak, and hBTT, that is, the interval time between the first peak of the ultrasound and when this reaches the speed of 1,570 m/s, which is the velocity of ultrasound in the soft tissue. This latter parameter allows one to measure bone tissue independently of soft tissue. QUS measurements were also performed at the phalanges on all mothers (age range 24-38 years), who also completed a self-report questionnaire on their obstetric history, smoking and dietary habits and family history of osteoporosis. In 73 mothers and their children QUS was repeated after 12 months. All QUS parameters were slightly higher in male than in female newborn infants but the difference was not significant. BTT and hBTT of neonates showed a significant relationship with birth weight (r = 0.20; P < 0.05 and r = 0.37; P < 0.01, respectively) and with cranial circumference (r = 0.22; P < 0.05 and r = 0.36; P < 0.01, respectively). In newborn infants none of the QUS parameters was significantly influenced by maternal QUS or by maternal smoking and calcium intake. In a model of multiple regression analysis the cranial circumference was the only parameter entered into the model, explaining approximately 15% of hBTT value. At month 12 AD-SoS and SoS were slightly lower than at birth (-11% and -0.1%, respectively), whereas both BTT and hBTT showed a significant (P < 0001) increase. The present study demonstrated the feasibility of the use of QUS, as assessed by a new measurement approach at the humerus, in the evaluation of skeletal status in neonates. BTT and, above all, hBTT, appears to be the best parameter for both evaluation of skeletal status at birth and monitoring of bone growth in the first year of life.

Alendronate treatment in men with primary osteoporosis: a three-year longitudinal study.

Bisphosphonates have been widely used in the treatment of osteoporosis in women, whereas until now there have been few data on their use in men. The aim of this study was to evaluate the effect of a 3-year alendronate treatment on bone mineral density (BMD) and quantitative ultrasound (QUS) in men with primary osteoporosis. We studied 77 osteoporotic men (aged 57.1 +/- 10.8 yrs) who completed a 3-year treatment with alendronate (10 mg/day) plus calcium (1000 mg/day) (n = 39), or calcium alone (n = 38). At baseline and at a 12-month interval, we measured BMD at the lumbar spine and femur (femoral neck and total hip) by DXA (Hologic) and speed of sound (SOS), broadband ultrasound attenuation (BUA) and Stiffness (S) at the os calcis by Achilles plus (Lunar). Alendronate treatment had significantly increased lumbar spine BMD by 4.2% at year 1, by 6.3% at year 2, and 8.8% at year 3. BMD at the femoral neck and total hip had increased by 2.1% and 1.6% at year 1, by 3.2% and 2.9% at year 2, and by 4.2% and 3.9% at year 3, respectively. BUA and Stiffness showed a significant increase in the alendronate-treated group at year 2 (3.2% and 4.9%, respectively) and at year 3 (3.8% and 6%, respectively). BMD at the lumbar spine showed the best longitudinal sensitivity whereas longitudinal sensitivity of both QUS at the heel and femur BMD were similar. In conclusion, this study confirms that alendronate represents an important therapeutic advance in the management of male osteoporosis. BMD at the lumbar spine appears to be the best method for monitoring the effect of alendronate on bone mass in osteoporotic men.

Definition of a population-specific DXA reference standard in Italian women: the Densitometric Italian Normative Study (DINS).

Osteoporosis is currently defined on the basis of the T-score by dual-energy X-ray absorptiometry (DXA). Despite its limitations, this definition is applied worldwide. However, the normal values provided by manufacturers may not be fully representative of specific local populations. So far, there are no normative data in the Italian population using Hologic densitometers. The Densitometric Italian Normative Study (DINS) is an ongoing multi-center study that aims to establish reference values for bone densitometry with dual-energy X-ray absorptiometry (DXA) in the male and female Italian population. In this paper we report the results of the lumbar vertebrae (L2-L4) and proximal femur in 1,622 women aged 20-79 years. Bone mineral density (BMD) was determined using dual-energy X-ray absorptiometry (DXA) on Hologic bone densitometers (Hologic, Waltham, Mass.). Most of the subjects were examined with a QDR 4500. The BMD of the lumbar vertebrae was virtually constant between 20 and 49 years (test for trend: P=0.66); the BMD values between 20-45 in premenopausal women (mean 1.036; SD 0.109 g/cm(2)) were thus defined as the peak bone mass values, significantly lower compared to the Hologic reference curve (mean 1.079, SD 0.11 g/cm(2)). The mean BMD values of the femoral neck were virtually identical to those of the NHANES study in the first 3 decades; after the age of 50 the BMD values were slightly greater than those of the NHANES subject. The subject classification according to the WHO criteria was similar using the DINS and NHANES reference values for the femur; for the spine, the Hologic reference values classified a larger proportion of women as osteoporotic (21 vs. 16%) or osteopenic (42 vs. 38%) compared to DINS.

A new serum assay to measure N-terminal fragment of telopeptide of type I collagen in patients with renal osteodystrophy.

BACKGROUND: Up until now, there was little known about the use of bone resorption markers in the assessment of bone status in patients with chronic renal failure (CRF). The present study evaluated the ability of a new immunoassay for N-terminal telopeptide of type I collagen to assess bone turnover in a group of hemodialyzed patients. METHODS: The following parameters were measured in a fasting blood sample from 111 patients on maintenance hemodialysis for at least 2 years and in 120 healthy subjects: calcium, phosphorus, magnesium, BALP, PTH, and N-terminal telopeptide of type I collagen (NTx-ELISA, OSTEOMARK NTx Siero-Ostex International). RESULTS: Serum PTH, BALP, and NTx were significantly higher (P<0.001) in hemodialyzed (HD) patients than in healthy subjects. In HD patients, PTH was correlated to BALP and NTx (r=0.40 and 0.55, respectively). When combining PTH and BALP serum levels, 17 patients showed high turnover (HT) and 65 were found to have a normal to low turnover (N-LT). In HT patients, serum NTx and dialytic age were significantly (P<0.01) higher than in N-LT patients. Moreover, even after adjusting for age, body mass index, dialytic age, and calcium-vitamin D treatment, serum NTx discriminated between HT and N-LT with a sensitivity of 97.6% and a specificity of 90.9%. CONCLUSION: Although bone biopsy remains the reference method for the diagnosis of renal osteodystrophy, the combined use of markers of bone resorption and bone formation could improve the clinical management of renal bone diseases.

Effect of simvastatin treatment on bone mineral density and bone turnover in hypercholesterolemic postmenopausal women: a 1-year longitudinal study.

Although several studies have reported a lower risk of osteoporotic fracture in hypercholesterolemic patients treated with statins, so far longitudinal studies on the effects of statins on bone are lacking. The aim of the present study was to evaluate bone mineral density (BMD) and bone turnover changes induced by 1-year simvastatin treatment on postmenopausal women. Thirty consecutive postmenopausal hypercholesterolemic women (61.2 +/- 4.9 years) were treated for 12 months with 40 mg/day simvastatin and 30 normocholesterolemic age-matched postmenopausal women provided control data. In all subjects, at baseline and at 3-month intervals, serum lipids, calcium, phosphate, total and bone alkaline phosphatase (Bone-ALP), and carboxy-terminal fragment of type I collagen (CTx) were measured in a fasting blood sample. At baseline and after 6 and 12 months BMD was measured at lumbar spine (BMD-LS) and at femur (BMD-Ftot) and at femoral neck (BMD-Fn) by DXA. In the simvastatin-treated group Bone-ALP showed a significant increase (P < 0.05) with respect to baseline from the sixth month, whereas serum CTx showed a weak and nonsignificant increase over the study period. In treated women BMD-LS, BMD-Fn, and BMD-Ftot increased respectively by 1.1, 0.9, and 0.4% at Month 6; and by 2.8, 1.0, and 0.8% at Month 12. In controls BMD-LS, BMD-Fn, and BMD-Ftot at the end of the study period decreased by 1.6, 1.4, and 1.2%, respectively. The difference between controls and simvastatin-treated patients was significant (P < 0.05) for both BMD-LS and BMD-Fn only at Month 12. In conclusion our results, although obtained from a small sample of postmenopausal hypercholesterolemic women, suggest a probable positive effect of simvastatin on bone formation and BMD.

Changes in serum HDL and LDL cholesterol in patients with Paget's bone disease treated with pamidronate.

Amino bisphosphonates represent one of the most important advances in the management of Paget's and other metabolic bone diseases. Although their mechanism of action has not yet been completely clarified, they seem to inhibit the mevalonate pathway and so they could interfere with cholesterol synthesis. The present study aimed to evaluate cholesterol and lipoprotein serum levels in patients with Paget's bone disease treated with intravenous pamidronate. The study included 20 consecutive patients (mean age, 67.6 +/- 11.0 years) with Paget's bone disease for at least 1 year, who needed intravenous amino bisphosphonate treatment; 12 patients with inactive Paget's bone disease served as controls. The patients with active Paget's bone disease underwent three cycles (every 3 months) of treatment with 60 mg of intravenous pamidronate. Controls were given a saline infusion following the same administration schedule. In all subjects total alkaline phosphatase (total ALP), bone alkaline phosphatase (bone ALP), total cholesterol (TC), tryglycerides (TG), and high- and low-density lipoprotein cholesterol (HDL-C and LDL-C, respectively) were measured before infusions (pamidronate or saline) at baseline and at 3-month intervals up to 9 months. In the control group no significant changes were observed through the study period for any of the biochemical parameters. In the pamidronate-treated patients, both bone ALP and total ALP significantly fell at the end of the study. In patients with active treatment, at the end of the study period HDL-C significantly (P < 0.05) increased by 10.3%, whereas LDL-C significantly (P < 0.05) decreased by 5.5%. In these patients TC showed a negative trend without reaching statistical significance, whereas the HDL-C/LDL-C ratio rose 16.2% above the basal value and TC/HDL-C decreased by 12.5%. In conclusion, pamidronate given intravenously seems to be able to induce a prolonged shifting in circulating cholesterol from the LDL-C to the HDL-C from associated with a weak decrease in total cholesterol, thus producing a possible improvement in the atherosclerotic risk index.

Heel ultrasonography in monitoring alendronate therapy: a four-year longitudinal study.

The possibility of using quantitative ultrasound (QUS) in monitoring the response to antiresorptive drugs has yet to be defined. The aim of the present study was to evaluate whether heel ultrasonography, considering its characteristics of long-term precision, is able to monitor osteoporotic patients treated with alendronate. We studied 150 postmenopausal osteoporotic women (age 59.6 +/- 5.3 years) treated with alendronate and calcium (n = 74) or with calcium alone (n = 76) for 4 years. At baseline and after 12, 24, 36 and 48 months, we measured bone mineral density (BMD) at the lumbar spine by dual-energy X-ray absorptiometry (DXA, Hologic 4500), and speed of sound (SOS), broadband ultrasound attenuation (BUA) and Stiffness at the calcaneus by Achilles plus. Moreover, the longitudinal precision of QUS parameters was assessed by measuring 10 subjects once a month for 1 year and, on the basis of the coefficients of variation we obtained, we calculated the Least Significant Change between two measurements. In the alendronate-treated patients, at year 1, BMD increased by 4.2%, SOS by 0.4%, BUA by 1.1% and Stiffness by 3.2%; at year 2, BMD increased by 5.0%, SOS by 0.7%, BUA by 1.4% and Stiffness by 5.7%. At year 3, BMD increased by 6.2%, SOS by 0.9%, BUA by 1.8% and Stiffness by 7.6%. At the end of the study period, BMD increased by 7.6%, SOS by 1.2%, BUA by 1.9% and Stiffness by 9.0%. The minimal significant difference between two measurements was 0.8% for SOS, 5.6% for BUA and 5.0% for Stiffness. Among the QUS parameters, Stiffness showed the greatest total treatment effect and a longitudinal sensitivity which was only slightly lower than BMD. The MTI, which represents the period between scans required to show that a 'true' change has occurred, was 1.8, 2.7, 11.9 and 2.2 years for BMD, SOS, BUA and Stiffness respectively. Therefore, although the spinal BMD remains the optimal method, QUS at the heel, and in particular Stiffness, seems to be a sensitive tool for monitoring the response to alendronate.

Graphic trace analysis of ultrasound at the phalanges may differentiate between subjects with primary hyperparathyroidism and with osteoporosis: a pilot study.

Bone loss characterizes both primary hyperparathyroidism (PHPT) and osteoporosis (OP) but with a different histologic pattern, and this could partially explain the different fracture incidence in these two populations. Quantitative ultrasound (QUS), influenced by bone structural parameters other than bone mineral density (BMD), could evidence these differences, opening new perspectives in the evaluation of patients with metabolic bone diseases. The aim of the present study was to investigate the usefulness of QUS graphic trace parameters, assessed at the phalanx, in discriminating between PHPT bone disease and osteoporosis. We studied 34 patients with PHPT (mean age 59.7 +/- 12.7 years), 35 patients with OP (mean age 60.6 +/- 7.1 years) and 34 healthy subjects as controls (mean age 59.1+/- 9.4 years). In all subjects QUS measurements were performed at the phalanx with a Bone Profiler (IGEA, Italy), obtaining the amplitude-dependent speed of sound (AD-SoS), fast wave amplitude (FWA), signal dynamic (SDy), bone transmission time (BTT) and ultrasound bone profile index (UBPI). Moreover, serum calcium, phosphorus, parathyroid hormone (PTH), bone isoenzyme of alkaline phosphatase (B-ALP) and ionized calcium were measured in all subjects in the morning under fasting conditions. In PHPT patients BTT was correlated with PTH, ionized calcium and B-ALP levels (r = -0.47, -0.57 and -0.44, respectively; p < 0.01), whereas FWA, SDy and UBPI correlated only with B-ALP (r = -0.43, -0.46 and -0.50, respectively; p <0.01). Moreover, FWA, SDY and UBPI were significantly (p<0.01) lower and BTT significantly (p<0.001) higher in OP than in PHPT patients. UBPI, BTT, FWA and the BTT/FWA ratio, but not SDy, were able to discriminate between the two groups (area under the curve =0.66, 0.69, 0.67 and 0.81, respectively). Our findings show that ultrasound signal parameters are differently influenced by bone changes characterizing primary hyperparathyroidism or osteoporosis. This suggests that the QUS signal could be a useful instrument in discriminating and studying some of the bone alterations typical of metabolic bone diseases.

The use of ultrasound in the assessment of bone status.

The assessment of skeletal status has wide clinical applications, especially in the management of osteoporosis. Osteoporosis, once thought of as an unpreventable and untreatable aging process, has revealed many of its secrets over the last decade, and the advent of successful drug therapy has changed our perception of the disease. Non-invasive techniques play a fundamental role in the diagnosis of osteoporosis and in the assessment of the efficacy of drug treatments. The primary technique used in osteoporosis is dual X-ray absorptiometry (DXA), that has been established as a reliable means of measuring bone density. Quantitative ultrasound (QUS), because of the relative portability of the equipment, ease of use, lack of ionizing radiation and low cost, has great potential for widespread use. Five devices for QUS assessment have recently been approved by the Food and Drug Administration and many more applications are in progress. QUS is a relatively new technology, at least in its application to bone fragility. Nevertheless, QUS has demonstrated that it is able to detect bone fragility as well as DXA. However, diagnosis of osteoporosis by QUS remains contentious, but the problems are due more to the limitations of the present T-scores rather than to the technique. A better option for QUS would be to report results in terms of remaining lifetime fracture risk, keeping in mind that a risk estimate needs not only the QUS or DXA measurement, but also the specific data, such as age, weight, gender, hormonal status and fracture history of the patient.

Usefulness of bone quantitative ultrasound in management of osteoporosis in men.

In order to evaluate the usefulness of QUS at the phalanx in the diagnosis of osteoporosis and in the prediction of fracture risk in males. The study consisted of 182 subjects (age 61.2 +/- 9.4 yr), of which 22 had had a previous nontraumatic bone fracture. In all subjects, bone mineral density (BMD) at the lumbar spine and femur was measured by DXA. Moreover, in the same subjects, QUS parameters, the amplitude-dependent speed of sound (AD-SOS), and the parameters characterizing the graphic trace (fast-wave amplitude, signal dynamic, and bone transmission time [BTT]) were assessed at the phalanxes using the DBM Sonic 1200 (IGEA). According to World Health Organization (WHO) criteria, all the patients were divided into two groups: 62 osteoporotic subjects and 120 nonosteoporotic subjects. All QUS parameters were significantly lower in osteoporotic than in nonosteoporotic patients. Receiver operating characteristic (ROC) analysis showed a moderate ability of AD-SOS, BTT, and ultrasound bone profile index (UBPI) in distinguishing between healthy and osteoporotic men. Among osteoporotic patients, BMD values were lower in patients with fracture than in those without fracture. AD-SOS and BTT were significantly reduced in men with fracture. Furthermore, in a regression analysis, only BTT and DXA parameters were predictive of fracture. Moreover, performing a multivariate regression analysis BTT entered before BMD at the lumbar spine and at Ward's triangle. In conclusion, our data show that QUS parameters are reduced in osteoporotic males; however, only BTT was comparable to DXA parameters in the prediction of fracture risk in men.

Dual X-ray absorptiometry and bone ultrasonography in patients with Rett syndrome.

This study evaluated bone status and bone turnover in 82 females (ages 2-21 years) with the Rett Syndrome (RS) and 82 age-matched controls. Bone mineral density (BMD) by dual X-ray absorptiometry (DXA) at the ultradistal and proximal radius and ultrasonographic (QUS) parameters at the calcaneus [speed of sound(SOS), broadband ultrasound attenuation(BUA), and stiffness] and at the phalanxes (amplitude dependent speed of sound: AD-SOS) were measured. We also measured serum calcium, phosphate, 25-hydroxyvitamin D, and biochemical markers of bone turnover. DXA and QUS parameters were significantly lower in patients with RS compared with controls and, among RS alone, in those treated with anticonvulsants and in those who are nonambulatory. Ambulatory RS patients showed QUS and DXA parameters significantly greater than nonambulatory patients but significantly lower than controls. Patients with RS treated with anticonvulsants presented QUS and DXA parameters lower than those of other RS. In RS patients, walking significantly influences BMD-UD, BMD-P, SOS. BUA. and Stiffness. Serum 25-hydroxyvitamin D was significantly lower in RS than in controls. These results suggest that ambulatory status, to a major extent, and anticonvulsant therapy certainly play an important role in the reduction of bone mass and bone quality, but they cannot completely explain the altered bone status. Whatever the cause, girls with RS present abnormal bone status with an increase in the risk of fracture.

Quantitative ultrasound at the phalanges in healthy Italian men.

In the last decade there has been a growing interest in quantitative ultrasound (QUS) techniques as a new method in the assessment of bone status in metabolic bone diseases. Many studies have shown that QUS parameters can predict vertebral and femoral fracture risk in patients with osteoporosis. However, most of the studies were performed in women, whereas few data are available for men. The aim of this study was to build up a normative database on a healthy Italian male population for QUS parameters at the phalanges. Amplitude-dependent speed of sound (AD-SoS) and three parameters (first wave amplitude, FWA; signal dynamic, SDy; time frame, TF) characterizing the graphic trace of the ultrasound signal were measured at the phalanges in 286 healthy subjects (age range 20-87 years). First, the QUS device was adapted to compensate for the difference in finger thickness between men and women. Preliminary data on 150 healthy subjects showed a significant difference between the traditional and adapted device, and the latter was independent of finger thickness variations. AD-SoS showed a significant (p<0.001) decrease with aging, expressed by a second-order polynomial equation. The peak value (2122 m/s) was observed in the fourth decade; thereafter it decreased to 1980 m/s at the ninth decade. Likewise, FWA and SDy were significantly (p<0.001) reduced after the fourth decade, whereas TF remained stable over time until the last decade. In conclusion, in men AD-SoS showed a negative trend with aging. The pattern with aging of parameters characterizing the graphic trace was different from the pattern for AD-SoS, suggesting the possibility of obtaining further information on phalanx bone physical properties which could be useful in the differential diagnosis of metabolic bone diseases and in the assessment of fracture risk.

Quantitative ultrasound and bone mineral density in patients with primary hyperparathyroidism before and after surgical treatment.

The aim of this study was to assess the pattern of ultrasound (QUS) parameters and bone mineral density at different skeletal sites in patients with primary hyperparathyroidism (PHPT) before and after surgical treatment. In 22 patients (age range 28-74 years) with PHPT we measured speed of sound (SOS), attenuation (BUA) and Stiffness at the calcaneus, amplitude-dependent speed of sound (AD-SoS) at proximal phalanges, and bone mineral density at lumbar spine (BMD-LS) and at the mid-radius (BMD-MR) and ultra-distal radius (BMD-UDR) before, 1 and 2 years after surgical operation. Twenty-two age- and sex-matched healthy subjects provided control data. Before surgery, all parameters apart from SOS were significantly lower in PHPT patients than in controls. At the end of the study period, BMD-LS increased by 7.0%, BMD-UDR by 7.4% and BMD-MR by 11.0%. The changes in ultrasound parameters after surgery were lower (0.44% for SOS, 2.2% for BUA, 3.3% for Stiffness and 2.6% for AD-SoS); however, the increase was statistically significant (p < 0.05 and p < 0.01, respectively) only for Stiffness and AD-SoS. Our results indicate that parathyroidectomy increases both axial and appendicular BMD and influences QUS parameters differently at the calcaneus and at the phalanges. The combined use of BMD and QUS could improve the assessment of skeletal status in patients with PHPT before and after surgery.

Bone turnover and the response to alendronate treatment in postmenopausal osteoporosis.

This study investigated whether bone turnover influences the response to alendronate in women with postmenopausal osteoporosis. One hundred postmenopausal osteoporotic women were randomized to receive either alendronate (10 mg/day) plus calcium (1000 mg/day) (n = 50) or calcium alone (n = 50). Vertebral and radial bone density, measured by DXA, and markers of bone turnover were assessed at baseline and after 1 and 2 years. At the end of treatment, alendronate users showed an increase of 5.0% and 2.3%, respectively, at the lumbar spine and ultradistal radius; in the group treated only with calcium, bone mineral density (BMD) decreased by 1.6% at the lumbar spine and 1.3% at the ultradistal radius. The difference between the two groups was significant (P < 0.001). The patients were divided into high (HT) or low (LT) bone turnover groups, as assessed by 24-hour whole body retention (WBR%) of (99m)Tc-methylene-diphosphonate. The response to alendronate treatment was greater in HT patients compared with LT patients. In fact, at the end of the study period, BMD at the lumbar spine had increased by 7.9% in HT patients and by 3.0% in LT patients; the difference between the two groups was significant (P < 0.001). No significant difference between the two groups was found for BMD at the ultradistal radius. In conclusion, the present study demonstrates that 2-year treatment with alendronate has highly positive effects on bone mass at both the lumbar spine and ultradistal radius. The increase in bone mass, especially at the axial level, is influenced by bone turnover. Therefore, the evaluation of bone turnover may be useful in predicting the response to alendronate treatment.

FokI polymorphism at translation initiation site of the vitamin D receptor gene predicts bone mineral density and vertebral fractures in postmenopausal Italian women.

A novel T/C polymorphism (ATG to ACG) at the translation initiation site of the vitamin D receptor (VDR) gene, defined by FokI restriction endonuclease, has been recently associated with variation in bone mineral density (BMD) and rates of bone loss in a group of postmenopausal Mexican-American women. The presence of the restriction site, designated as f, allows protein translation to initiate from the first ATG, while the allele lacking the site, indicated as F, initiates translation at a second ATG. In this study, we investigated the role of FokI polymorphism in a group of 400 postmenopausal women of Italian descent stratified for BMD into osteoporotic (n = 164), osteopenic (n = 117), and normal (n = 119) groups. There were 159 (41%) FF homozygotes, 55 (14%) ff homozygotes, and 186 (45%) Ff heterozygotes. In the whole population, we observed a weak association between FokI polymorphism and lumbar BMD (p = 0.06, analysis of covariance [ANCOVA]) but not with femoral neck BMD (p = 0.5, ANCOVA). Interestingly, the effect of FokI genotypes on lumbar BMD was influenced by the years since menopause such that differences in BMD related to different VDR allelic variants were greater among women in the first 5 years of menopause (p = 0.04, ANCOVA), progressively declining afterward. In addition, a significantly higher prevalence of ff genotype in osteoporotic than in osteopenic and normal women was observed (p = 0.04, Chi-square test). Finally, ff genotype resulted significantly over-represented in the group of women with a vertebral fracture as compared with controls (p = 0.003, Chi-square test), equivalent to a relative risk of 2.58 (95% confidence intervals 1.36-4.91). We conclude that in this population, FokI polymorphism at the VDR gene locus accounts for a part of the heritable component of BMD at the lumbar spine.

Osteogenesis imperfecta: bone turnover, bone density, and ultrasound parameters.

We studied 21 patients (11 men and 10 women) with osteogenesis imperfecta (OI) and 21 age- and sex-matched controls. In all patients we measured serum levels of total alkaline phosphatase (ALP), type I procollagen carboxy-terminal propeptide (PICP), osteocalcin (BGP), urinary excretion of hydroxyproline (HOP/Cr), and pyridinoline crosslinks (Pyr/Cr). Bone mineral density was measured at the distal radius (BMD-R) and at the lumbar spine (BMD-LS) by dual X-ray absorptiometry (DXA). Ultrasound parameters were also performed at the calcaneous with the Achilles device and at the phalanxes with DBM Sonic 1200. A significant reduction (P < 0.001) in BMD and in ultrasound parameters was found in OI patients compared with normals. PICP was significantly reduced in the OI patients compared with controls (P < 0.001); other markers of bone turnover were higher in OI than in controls, but the difference did not reach the statistical significance. A significant correlation (P < 0.05) was found between PICP and BMD at the lumbar spine and between PICP and ultrasound parameters at the calcaneous. On the basis of our data, we conclude that patients with OI show low values of BMD and ultrasound parameters; therefore in these patients, not only is bone mass disturbed but also bone quality. The reduced levels of PICP in OI patients confirm that most OI patients have defects in collagen I biosynthesis. These defects may contribute to the fragility of OI bone by interfering with complete mineralization and/or normal tissue structure. PICP may be considered a useful marker in the clinical management of OI.