Biomedical subjects

S Gonnelli

Publications and source records attributed to S Gonnelli.

At least 55 records · Page 3Linked to original sources

PubMed1998

Vitamin D and estrogen receptor allelic variants in Italian postmenopausal women: evidence of multiple gene contribution to bone mineral density.

Bone mass and bone turnover are under genetic control. Restriction fragment length polymorphisms (RFLPs) at the vitamin D receptor (VDR) gene locus have been recently correlated to bone mineral density (BMD) and rate of bone loss. However, agreement on this relationship is not universal. The existence of ethnical and environmental differences between populations, a health-based selection bias in several previous studies, and the involvement of other genes could explain these discordant findings. In this study, we examined the relationship of VDR and estrogen receptor (ER) gene RFLPs with lumbar spine and upper femur BMD in 426 Italian postmenopausal women, 57.7 +/- 0.4 yr old (144 normal, 106 osteopenic, and 176 osteoporotic). VDR gene RFLPs for ApaI, Bsm I, and TaqI restriction endonucleases and ER RFLPs for PvuII and XbaI restriction endonucleases were assessed by Southern blotting analysis and were indicated, respectively, as A-a, B-b, T-t, P-p, and X-x (uppercase letters signifying the absence and lowercase letters the presence of the restriction site). After correcting for potential confounding factors (age, height, weight, age since menopause, osteophytosis, and facet joint osteoarthritis), a statistically significant VDR genotype effect on lumbar BMD (P = 0.01, analysis of covariance), but not on femoral BMD, was detected, with subjects in AABBtt genotype showing a 13% lower BMD than those with aabbTT genotype (P < 0.05, Tukey's test). Moreover, a statistically significant prevalence of AABBtt genotype in osteoporotics, and of AabbTT and aabbTT genotypes in nonosteoporotics, were detected. Conversely, there was no significant relationship of ER genotype to either lumbar or femoral BMD, even though a trend for higher BMD values in women with the ER PP genotype (with respect to those with ER pp genotype) was detected. When mean lumbar BMD was calculated for women grouped by ER and VDR genotype, we observed a significant difference between those within the 2 opposite associations AABBtt-PPXX and aabbTT-ppxx (0.71 +/- 0.05 vs. 0.97 +/- 0.03 g/cm2, P < 0.05 Tukey's test). These results are consistent with a segregation of the VDR AABBtt genotype with a higher risk of developing osteoporosis, in the Italian female population. The introduction of another variable, the ER genotype, in the analysis of VDR genetic determination of BMD, may represent a useful model in the identification of patients at risk of developing a multigenic disorder like osteoporosis.

Alleles↗

PubMed1997

Prevention of corticosteroid-induced osteoporosis with alendronate in sarcoid patients.

Prolonged corticosteroid administration, as often required in the treatment of sarcoidosis, increases the risk of osteoporosis and fracture. The aim of the present study was to evaluate the usefulness of alendronate, a third generation bisphosphonate, in preventing corticosteroid-induced osteoporosis. Forty-three consecutive, previously untreated, sarcoid patients (17 men and 26 premenopausal women) were included in the study: 13 needed no treatment and served as controls (Group 1) and 30 needed glucocorticoids (prednisone) and were randomly selected to also receive either placebo (n = 15, Group 2) or alendronate 5 mg/day (n = 15, Group 3). Bone mineral density (BMD) at the ultradistal radius by dual photon absorptiometry (Osteograph 1000, NIM, Verona, Italy) and biochemical markers of bone turnover were measured at baseline and after 6 and 12 months of glucocorticoid therapy. No significant difference was found between Groups 2 and 3 in the mean cumulative dose of prednisone (4945 +/- 1956 mg and 5110 +/- 2013 mg, respectively). At the end of the study period, BMD increased by 0.8% in the alendronate-treated group; in the placebo-treated group, BMD decreased by 4.5%. The difference between groups was significant (P < 0.01, ANOVA). A significant decrease in markers of bone formation was found in all patients treated with prednisone (Groups 2 and 3), independently of alendronate. Alendronate, however, counteracted the increase in markers of bone resorption induced by glucocorticoid therapy. Our data suggest that alendronate is effective in preventing glucocorticoid-induced bone loss in sarcoid patients. Further studies on alendronate use in steroid-induced osteoporosis are needed.

Absorptiometry, Photon↗

PubMed1997

Vitamin D receptor genotypes and intestinal calcium absorption in postmenopausal women.

Several studies have shown that bone mass and bone turnover are genetically determined. This genetic component is thought to be mediated in part by polymorphisms at the vitamin D receptor (VDR) locus, even though the underlying molecular mechanisms are still unknown. To evaluate a possible site of differential action of the VDR gene alleles we examined their correlation with intestinal calcium absorption in 120 Caucasian postmenopausal women (aged 61 +/- 0.6 years). VDR gene polymorphisms for Apa I, Bsm I, and Taq I restriction endonucleases were assessed by Southern blotting analysis. The most common genotypes observed in our population were AaBbTt (37%), AABBtt (20%), aabbTT (15%), AabbTT (15%), and AABbTt (9%). Although there was some evidence of 13% higher lumbar BMD values in aabbTT genotype with respect to AABBtt genotype, this difference of approximately 0.1 g/cm2 did not reach statistical significance, possibly because of the limited number of observations. On the contrary, no relationship was found between genotypes and femoral neck BMD values. Intestinal calcium absorption was significantly lower in BB and tt genotypes than, in bb and TT genotypes, respectively, and in AABBtt genotype than in either aabbTT or AaBbTt genotypes (P = 0.0015 ANOVA). No significant differences in intact PTH, alkaline phosphatase, 25OHD3, and 1, 25(OH)2D3 were found among subjects with different VDR genotypes. These results are consistent with a possible role of VDR alleles on intestinal calcium absorption.

Aged↗

PubMed1997

Paget's disease.

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Alleles↗

PubMed1997

Treatment of post-menopausal osteoporosis with recombinant human growth hormone and salmon calcitonin: a placebo controlled study.

OBJECTIVE: The usefulness of GH in the treatment of post-menopausal osteoporosis (PMO) is still debated. We have studied the effects of recombinant human GH (rhGH) given alone or in combination with salmon calcitonin (sCT) in the treatment of PMO. PATIENTS: Thirty women with established PMO (aged 61.1 +/- 4.4 years) were divided into 3 groups of 10 and randomly assigned to 3 treatment sequences: rhGH (12IU/day) s.c. for 7 days, followed by sCT (50 IU/day) s.c. for 21 days and by 61 days without treatment (group 1); placebo for 7 days, followed by sCT for 21 days and by 61 days without treatment (group 2); rhGH for 7 days, followed by placebo for 21 days, and by 61 days without treatment (group 3). Each cycle was repeated 8 times (24 months). MEASUREMENTS: At days 0, 8, 29 and 90 of each cycle, serum IGF-I, calcium, phosphate, osteocalcin, alkaline phosphatase and urinary excretion of calcium, hydroxyproline and pyridinoline cross-links (Pyr) were measured. At months 0, 6, 12, 18 and 24, bone mineral density (BMD) was measured by dualphoton absorptiometry (DPA), at lumbar spine (LS), femoral shaft (F) and distal radius (DR). RESULTS: A significant increase in serum osteocalcin and urinary calcium, hydroxyproline and Pyr was detected after each rhGH period. In group 1, BMD at lumbar spine increased by 2.5% at year 2; in contrast, significant (P < 0.05) decreases in BMD-LS values were found in patients treated with CT and placebo (group 2) and with GH and placebo (group 3). BMD-F did not show any significant change in patients of group 2, but a significant (P < 0.05) decrease was found in groups 1 and 3. BMD-DR did not show any significant change with respect to baseline in any of the three groups. No significant difference between the three groups was found in bone mass at the three different regions. CONCLUSIONS: Our study demonstrates that treatment with rhGH increases bone turnover in postmenopausal osteoporotic women. Combined treatment with rhGH and CT over a period of 24 months is able to maintain bone mass at lumbar spine and distal radius, but induces a decline at femoral shaft; therefore, it does not seem particularly useful in the therapy of post-menopausal osteoporosis.

Amino Acids↗

PubMed1997

Unusual clinical features and early brain MRI lesions in a family with cerebral autosomal dominant arteriopathy.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a recently described inherited disorder. The pathologic gene maps on chromosome 19. The clinical spectrum of the disease consists of recurrent strokes, migraine, transient ischemic attacks, mood changes, and dementia. We report a genetically assessed CADASIL family with atypical clinical presentations of epileptic seizures. In two asymptomatic family members there were early brain abnormalities on MRI. Our report expands the clinical spectrum of CADASIL and suggests that it is possibly an undiagnosed disorder.

Adult↗

PubMed1997

The combined use of ultrasound and densitometry in the prediction of vertebral fracture.

Measurement of ultrasonographic parameters provides information concerning not only bone density but also bone architecture. We investigated the usefulness of ultrasonographic parameters and bone mineral density for evaluating the probability of vertebral fracture. 397 postmenopausal women (59.1 +/- 6.0 years) with (n = 178) or without (n = 219) atraumatic vertebral fractures were studied. In all women, bone mineral density (BMD) of the lumbar spine was evaluated by dual X-ray absorptiometry (DXA) and speed of sound (SOS); broadband ultrasound attenuation (BUA) and Stiffness in the calcaneus were evaluated by an Achilles unit (Lunar Corporation). Ultrasonographic parameters and BMD were compared by examining the magnitude of the odds ratios, to determine which produces the highest estimate of the probability of odds of fracture, and by examining widths of the respective confidence intervals (CI) to show which estimate of odd ratio is the most precise. The relative risk of vertebral fracture, after adjusting for potential confounders, was 3.5 (CI 2.6-4.8) for BUA; 4.5 (CI 3.2-6.2) for SOS; 5.8 (CI 4.0-8.4) for Stiffness and 7.5 (CI 4.8-11.5) for BMD. Ultrasound (US) parameters were still significant independent predictors of vertebral fracture, even after adjusting for BMD. The relative risk of fracture for a simultaneous decrease by 1 SD of BMD and by 1 SD of each ultrasound parameter was 17.3 (CI 9.4-39.6) for BMD and SOS; 18.3 (CI 8.4-30.6) for BMD and BUA and 22.1 (CI 8.9-52.7) for BMD and Stiffness. Our data suggest that US and BMD provide complementary information which can be combined to improve estimates of vertebral fracture risk.

Age Factors↗

PubMed1997

The usefulness of bone turnover in predicting the response to transdermal estrogen therapy in postmenopausal osteoporosis.

Transdermal estrogen therapy is now an accepted form of treatment for postmenopausal osteoporosis. Ninety postmenopausal osteoporotic women were randomized to receive either transdermal estrogen (0.05 mg/day 17 beta-estradiol) and calcium (n = 45) or calcium alone (n = 45). The study period was 2 years. Bone mineral density (BMD) at the lumbar spine (by dual-energy X-ray absorptiometry [DXA]) and markers of bone turnover (alkaline phosphatase, osteocalcin, hydroxyproline, pyridinoline cross-links) were assessed at baseline and after 1 and 2 years. In the estrogen-treated group, BMD showed a significant increase (p < 0.001) both after 1 and 2 years, with a reduction in biochemical markers. To investigate the effectiveness of estrogen treatment of postmenopausal osteoporosis in relation to bone turnover, we also divided the patients on the basis of bone turnover, as assessed by measurement of whole body retention (WBR) of 99mTc-methylene diphosphonate. WBR revealed that 26 patients had high bone turnover (HT) and 55 had low bone turnover (LT). The response to estrogen was greater in the HT patients than in the LT patients; in fact BMD increased by 5.7 and 6.6% in HT patients and by 2.6 and 2.7% in LT patients after 1 and 2 years, respectively. In conclusion, the present study demonstrates that, while the BMD decreases in the patients treated with calcium alone, 2-year treatment with transdermal estrogen increases axial BMD and that the response to estrogen treatment is influenced by bone turnover. Therefore, the evaluation of bone turnover may be useful to identify those postmenopausal osteoporotic women who may especially benefit from treatment with estrogen.

Administration, Cutaneous↗

PubMed1996

Ultrasound parameters in osteoporotic patients treated with salmon calcitonin: a longitudinal study.

Speed of sound (SOS) and broadband ultrasound attenuation (BUA) of ultrasound (US) in bone have been proposed as alternatives to radiation-based methods for the quantitative assessment of osteoporosis. However, the usefulness of US in monitoring response to treatment in osteoporotic patients has yet to be defined. To compare US with bone mineral density (BMD), we studied 112 osteoporotic women (age range 50-64 years). Seventy-eight of them were treated with salmon calcitonin nasal spray (CT; 200 IU/day, 1 month on and 1 month off) and calcium (500 mg/day); 34 patients were given only calcium. One hundred and four women complied with treatment throughout the 2-year study period. At baseline and after 1 and 2 years we measured BMD at lumbar spine by dual-energy X-ray absorptiometry (DXA), and SOS, BUA and Stiffness index, by an Achilles ultrasound unit. Moreover, biochemical markers of bone turnover (alkaline phosphatase, osteocalcin and hydroxyproline) were also measured at baseline and after 6, 12 and 24 months. In the calcitonin-treated group at the end of the study period BMD had increased by 1.99%, SOS by 0.20%, BUA by 0.88% and Stiffness by 2.12%. By contrast in the calcium-treated group all parameters had decreased (BMD, -2.66%; SOS, -0.55%; BUA, -3.30%; Stiffness, -6.0%) by the end of the study period. The differences between groups were significant for BMD, SOS and Stiffness. At baseline a significant, but weak correlation was found between BMD and US parameters. The correlation coefficients between percentage changes at the end of the study period, in BMD and in SOS, BUA and Stiffness, were all significant (p < 0.001), being 0.41, 0.53 and 0.57 respectively. In conclusion, ultrasound measurements carried out in conjunction with BMD measurements will yield a more comprehensive assessment of skeletal status and may be helpful in monitoring the response to treatment in osteoporotic patients.

Administration, Intranasal↗

PubMed1996

Effect of calcium supplementation as a high-calcium mineral water on bone loss in early postmenopausal women.

It is generally agreed that an adequate calcium intake is necessary for the maintenance of bone health and that calcium supplementation reduces the rate of bone loss in postmenopausal women. Mineral waters are calorie free, and some, with relatively high calcium levels, might be significant sources of calcium. We studied the effect of mineral water in 45 early postmenopausal women randomly assigned to receive a high-calcium (Ferrarelle, Italy) or a low-calcium mineral water. On the basis of the dietary regimen, women were divided in two clusters (A = 23 subjects, B = 22 subjects) significantly different only for calcium intake (CI) and for dietary consumption of calories (energy). At the end of the study period (13 +/- 1 months), bone mineral density at the distal radius showed a significant decrease (P < 0.001) only in cluster with low CI. The difference between the clusters was significant (P < 0.05). Furthermore, the cluster with high CI showed a significant (P < 0.05) reduction in osteocalcin serum levels after 3 months. This study provides further evidence to support the use of a high calcium mineral water as an effective prophylaxis against postmenopausal bone loss.

Calcium, Dietary↗

PubMed1996

Bone alkaline phosphatase measured with a new immunoradiometric assay in patients with metabolic bone diseases.

We have investigated the clinical utility of a new quantitative two-site radioimmunometric assay specific for bone alkaline phosphatase (B-ALP) in 219 healthy control subjects and in 264 patients with various metabolic bone diseases. B-ALP was compared with total alkaline phosphatase (T-ALP) and with osteocalcin (BGP). B-ALP increased linearly with age in both sexes. In postmenopausal normal women B-ALP increased by 82% compared with premenopausal normal women, whereas the differences between pre- and postmenopausal women for T-ALP and BGP were 18% and 30% respectively. As assessed by Z-score, the highest values of B-ALP were found in patients with Paget's disease of bone, bone metastases or hyperparathyroidism and in patients on maintenance haemodialysis. In osteoporotic patients, B-ALP< but not T-ALP, showed a slight but significant (P < 0.05) difference compared with normal women. On the basis of bone turnover, osteoporotic patients were divided into two groups: high turnover and low turnover; B-ALP, like BGP, was significantly (P < 0.01) higher in patients with high turnover. In conclusion, B-ALP, measured by this new method, can be considered a sensitive marker of bone turnover and could be especially useful in identifying women at risk of developing osteoporosis.

Adult↗

PubMed1996

[The efficacy and safety of glucosamine sulfate in the treatment of gonarthritis].

This study was performed to evaluate the therapeutic efficacy and tolerability of glucosamine sulfate in patients with gonarthritis. During the 12-month study period, the signs and symptoms of the disease were evaluated, as well as the dosage of the urinary pyridinoline. In this trial, we demonstrated that glucosamine sulfate has a chondroprotective activity, which was significant after the first 3 months of therapy. Moreover, this study showed that the side effects due to glucosamine sulfate were mild to moderate and did not require discontinuation of the drug.

Adult↗

PubMed1996

Tolerability of nabumetone: a pilot in vitro study showing absence of injury to articular cartilage.

Nabumetone, a compound of the naphthylalkanone class, has shown considerable anti-inflammatory, analgesic and antipyretic effects, together with high systemic and organ-specific tolerability. Its reputation for tolerability has been increased by an in-vitro study evaluating the mature collagen metabolism's markers under nabumetone treatment, which shows that, nabumetone does not interfere with collagen synthesis. Therefore, unlike some nonsteroidal anti-inflammatory drugs, nabumetone might not be injurious to articular cartilage. This feature makes nabumetone even safer for long-term treatment of rheumatic and orthopaedic conditions.

Adult↗

PubMed1995

Acute biochemical variations induced by two different calcium salts in healthy perimenopausal women.

Despite the potential utility of calcium supplementation and the availability of many calcium supplements in the market, there are few data concerning the absorbability of different calcium salts in different conditions. We have compared the acute metabolic responses following oral administration of calcium citrate (CC) or calcium gluconolactate and carbonate (CGC) given to 20 healthy perimenopausal women (aged 48-55 years). Ten women received two effervescent tablets of CC (each containing 500 mg of calcium) and 10 women received two effervescent tablets of CGC (each containing 500 mg of calcium). Before and on an hourly basis for 6 hours, serum total and ionized calcium, phosphate, and immunoreactive parathyroid hormone (iPTH) were measured. Urinary calcium and creatinine were also measured. Both calcium salts induced significant increase in serum total and ionized calcium and in urinary calcium excretion; they also significantly reduced circulating levels of iPTH. The analysis of ionized calcium and iPTH response curves to CC and CGC administration revealed a significantly greater bioavailability of CC compared with CGC. Our data suggest that CC could be prefered to CGC for its characteristics of absorbability and bioavailability.

Calcium↗

PubMed1995

Diagnostic value of ultrasound analysis and bone densitometry as predictors of vertebral deformity in postmenopausal women.

Bone fractures depend not only on bone density, but also on bone quality. Ultrasound (US) has been proposed as a technique for evaluating skeletal status. Speed of sound (SOS) and broadband ultrasound attenuation (BUA) are the US properties currently used to assess bone strength and fragility. In 304 postmenopausal women (age 58.8 +/- 5.5 years) we measured: bone mineral density (BMD) of the lumbar spine (by dual-energy X-ray absorptiometry), SOS, BUA and Stiffness in the os calcis (using an Achilles machine). In all subjects we performed lateral lumbar and thoracic radiographs. Morphometric parameters were derived by measuring the anterior, middle and posterior height of each vertebral body, to obtain a semiquantitative grading of vertebral fractures as follows: 0, no vertebral deformity; 1, any vertebral height reduced between 20% and 25%; 2, any vertebral height reduced between 25% and 40%; 3, any vertebral height reduced more than 40%. On the basis of the number and severity of vertebral deformities the women were divided into: group 1 (n = 79), normal; group 2 (n = 80), mild; group 3 (n = 85), moderate; and group 4 (n = 60), severe. Mean values of SOS, BUA, Stiffness and BMD were significantly lower (p < 0.001) in women with vertebral deformity than in normals. In the whole population SOS, BUA and Stiffness values were significantly correlated with BMD. SOS, BUA and Stiffness values were significantly decreased (p < 0.001) with vertebral deformity, as was BMD. Receiver operating characteristic (ROC) curve analysis showed BMD to be slightly better than Stiffness in discriminating among groups. Logistic regression analysis showed that BMD, BUA, SOS and Stiffness were independent predictors of vertebral fracture risk. Ultrasound parameters were still significant independent predictors of vertebral fracture even after adjusting for BMD.

Absorptiometry, Photon↗

PubMed1995

Ultrasonographic assessment of bone in normal Italian males and females.

Recently ultrasound techniques have been proposed to evaluate skeletal status. Speed of sound and attenuation through the bone are the ultrasound properties currently used to assess bone strength and fragility. The speed of sound in m s-1 (SOS), broadband ultrasound attenuation in dB MHz-1 (BUA) and stiffness (S) in 134 healthy females (age range 10-90 years) and in 100 healthy males (age range 10-93 years) was measured using the Achilles scanner (Lunar Corp., Madison, WI, USA). A polynomial function was applied to the observed data to evaluate a pattern of age-related BUA, SOS and S changes. Peak values of SOS, BUA and S were reached in both sexes at the age of 30 years. Average decreases of 12.9% in BUA, 4.9% in SOS and 28.9% in S were found in men aged between 30 and 90 years. In women average decreases of 17.2% in BUA, 4.2% in SOS and 31.9% in S were discovered in those aged between 30 and 90 years. The analysis of SOS, BUA and S changes between pre- and post-menopausal women revealed a significant decrease of these parameters with years since menopause. These data indicate an age-related decrease of ultrasound signals in both sexes. Furthermore, this technique is able to detect, in females, menopause related changes due to oestrogen failure. In contrast, in males, the age-related loss of ultrasound signals appears to be more linear.

Adolescent↗

PubMed1995

Hypertension and primary hyperparathyroidism: the role of adrenergic and renin-angiotensin-aldosterone systems.

Primary hyperparathyroidism (HPTH) is frequently associated with hypertension. To date, the relationship between these two conditions is still not clear. We have studied 34 consecutive patients with primary HPTH due to a parathyroid adenoma. The diagnosis was later surgically confirmed in 32 cases. Ten of thirty-four HPTH patients were hypertensive. Before adenomectomy (PTHX) and 1-2 months after PTHX, we measured the following parameters in all patients: circulating levels of total and ionized Ca, intact immunoreactive parathormone (iPTH) (1-84), plasma renin activity (PRA), aldosterone, and daily total urinary catecholamine excretion. Moreover, 10 hypertensive HPTH patients, 10 normotensive HPTH patients, compared to 10 to 10 sex- and age-matched healthy normotensive subjects, underwent an acute norepinephrine test to assess vascular reactivity to a pressor agent. Before PTHX, no significant difference was observed between normotensive and hypertensive patients in all the above-mentioned variables, except for PRA and plasma aldosterone levels which were higher in hypertensive patients. Furthermore, the pressor response to the norepinephrine test was significantly greater in hypertensive HPTH patients than in the other 2 groups. After PTXH, serum Ca and intact iPHT (1-84) levels were reduced to normal values in all patients, while blood pressure, PRA and plasma aldosterone levels became normal in 8 of 10 hypertensive patients. The pressor response to the norepinephrine test was similar in the 2 groups. These results are consistent with the hypothesis of a direct effect of PTH on renin secretion which could contribute to the pathogenesis of hypertension and to the vessels sensitization to pressor agents.

Adenoma↗

PubMed1993

Hypercalcemia in breast cancer.

Hypercalcemia is relatively frequent in malignancy with or without osteolytic bone metastases. It is thought that neoplastic cells may secrete substances which not only stimulate osteoclastic activity but are also capable of modifying the absorption, excretion, and resorption of calcium and phosphate ions. Since 1987, we have studied 24 breast cancer patients with hypercalcemia (22 with bone metastases and two without). The group of 22 patients with bone metastases were divided into two subgroups. The first consisted of 10 patients with high serum levels of humoral factors, such as parathyroid hormone-related protein (PTHrP), and/or prostaglandin E2 (PGE2) and/or interleukin 1 (IL-1), and high levels of bone markers, such as alkaline phosphatase, bone Gla protein and urinary hydroxyproline. The second subgroup consisted of 12 patients with high levels of bone markers alone. Bone histologic analysis showed an osteoclastic activation surrounding metastatic tumor tissue in six out of 10 patients of the first subgroup, while an evident osteolysis caused by the tumor cells was noted in seven out of 12 patients of the second subgroup. The two patients without bone metastases showed normal biochemistry and bone histologic examination. The authors, having tried to explain the pathogenesis of hypercalcemia, emphasize the importance of humoral factors secreted by tumor cells as a direct or indirect cause of hypercalcemia. The origin of hypercalcemia remains unclear in two patients without bone metastases.

Bone Neoplasms↗