The effect of 8 or 5 years of denosumab treatment in postmenopausal women with osteoporosis: results from the FREEDOM Extension study.

UNLABELLED: The FREEDOM study and its Extension provide long-term information about the effects of denosumab for the treatment of postmenopausal osteoporosis. Treatment for up to 8 years was associated with persistent reduction of bone turnover, continued increases in bone mineral density, low fracture incidence, and a favorable benefit/risk profile. INTRODUCTION: This study aims to report the results through year 5 of the FREEDOM Extension study, representing up to 8 years of continued denosumab treatment in postmenopausal women with osteoporosis. METHODS: Women who completed the 3-year FREEDOM study were eligible to enter the 7-year open-label FREEDOM Extension in which all participants are scheduled to receive denosumab, since placebo assignment was discontinued for ethical reasons. A total of 4550 women enrolled in the Extension (2343 long-term; 2207 cross-over). In this analysis, women in the long-term and cross-over groups received denosumab for up to 8 and 5 years, respectively. RESULTS: Throughout the Extension, sustained reduction of bone turnover markers (BTMs) was observed in both groups. In the long-term group, mean bone mineral density (BMD) continued to increase significantly at each time point measured, for cumulative 8-year gains of 18.4 and 8.3 % at the lumbar spine and total hip, respectively. In the cross-over group, mean BMD increased significantly from the Extension baseline for 5-year cumulative gains of 13.1 and 6.2 % at the lumbar spine and total hip, respectively. The yearly incidence of new vertebral and nonvertebral fractures remained low in both groups. The incidence of adverse and serious adverse events did not increase over time. Through Extension year 5, eight events of osteonecrosis of the jaw and two events of atypical femoral fracture were confirmed. CONCLUSIONS: Denosumab treatment for up to 8 years was associated with persistent reductions of BTMs, continued BMD gains, low fracture incidence, and a consistent safety profile.

Zoledronic acid results in better health-related quality of life following hip fracture: the HORIZON-Recurrent Fracture Trial.

UNLABELLED: This study evaluated the benefits of ZOL versus placebo on health-related quality of life (HRQoL) among patients from HORIZON-RFT. At month 24 and end of the study visit, ZOL significantly improved patients' overall health state compared to placebo as assessed by the EQ-5D VAS. INTRODUCTION: To evaluate the benefits of zoledronic acid (ZOL) versus placebo on health-related quality of life (HRQoL) among patients from The Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly Recurrent Fracture Trial (HORIZON-RFT). METHODS: In this randomized, double-blind, placebo-controlled trial, 2,127 patients were randomized to receive annual infusion of ZOL 5 mg (n = 1,065) or placebo (n = 1,062) within 90 days after surgical repair of low-trauma hip fracture. HRQoL was measured using EQ-5D Visual Analogue Scale (VAS) and utility scores (EuroQol instrument) at months 6, 12, 24, 36, and end of the study visit. Analysis of covariance model included baseline EQ-5D value, region, and treatment as explanatory variables. RESULTS: At baseline, patients (mean age 75 years; 24% men and 76% women) were well matched between treatment groups with mean EQ-5D VAS of 65.82 in ZOL and 65.70 in placebo group. At the end of the study, mean change from baseline in EQ-5D VAS was greater for ZOL vs. placebo in all patients (7.67 ± 0.56 vs. 5.42 ± 0.56), and in subgroups of patients experiencing clinical vertebral fractures (8.86 ± 4.91 vs. -1.69 ± 3.42), non-vertebral fractures (5.03 ± 2.48 vs. -1.07 ± 2.16), and clinical fractures (5.19 ± 2.25 vs. -0.72 ± 1.82) with treatment difference significantly in favor of ZOL. EQ-5D utility scores were comparable for ZOL and placebo groups, but more patients on placebo consistently had extreme difficulty in mobility (1.74% for ZOL vs. 2.13% for placebo; p = 0.6238), self-care (4.92% vs. 6.69%; p = 0.1013), and usual activities (10.28% vs. 12.91%; p = 0.0775). CONCLUSION: ZOL significantly improves HRQoL in patients with low-trauma hip fracture.

Epidemiology of hip fracture in Tucuman, Argentina.

UNLABELLED: The incidence of osteoporotic hip fracture was studied previously in a central area of Argentina. Studying Tucuman (north area) was very useful to compare results of the different areas and detect a similar incidence in women and a slightly higher incidence in men compared with previous data for the central region. INTRODUCTION/METHODS: Epidemiology of hip fracture was studied over a 1-year period in the city of San Miguel de Tucumán (SMT) and in the whole province of Tucumán, located in the northeast of Argentina (latitudes 26° and 28° south). The results were compared with previous studies performed in the central region of Argentina. RESULTS: Two hundred and eighty-three patients (208 women and 75 men) aged 50 years or over in SMT suffered a hip fracture. The incidence in females and males was 334.9 and 163.8 hip fractures per 100,000 inhabitants per year, respectively (female/male ratio 2.0). A total of 498 hip fractures were recorded in Tucuman province (367 in women and 131 in men). The results in females and males were 276.5 and 114.7 hip fractures per 100,000 inhabitants per year, respectively. Average age of the female and male population was 78±9 and 77±9 years, respectively. CONCLUSIONS: These results showed that the incidence of hip fracture in female and male populations in SMT was similar to previous studies performed in the central area of the country. Further studies on the south area of Argentina should be conducted to complete the information on a large country extending from latitudes 22° to 55°S.

Vitamin D2 dose required to rapidly increase 25OHD levels in osteoporotic women.

OBJECTIVE: Assessment of the effectiveness and safety of high daily 125 microg (5,000 IU) or 250 microg (10,000IU) doses of vitamin D(2) during 3 months, in rapidly obtaining adequate 25 hydroxyvitamin D (25OHD) levels. DESIGN: Longitudinal study. SUBJECTS: Postmenopausal osteopenic/osteoporotic women (n = 38) were studied during winter and spring. Median age (25-75th percentile) was 61.5 (57.00-66.25) years, and mean bone mineral density (BMD) was 0.902 (0.800-1.042)g/cm(2). Subjects were randomly divided into three groups: control group (n=13): no vitamin D(2), 125 mug/day (n=13) and 250 microg/day (n=12) of vitamin D(2) groups, all receiving 500 mg calcium/day. Serum calcium, phosphate, bone alkaline phosphatase (BAP), C-telopeptide (CTX), 25OHD, mid-molecule parathyroid hormone (mmPTH), daily urinary calcium and creatinine excretion were determined at baseline and monthly. RESULTS: For all subjects (n=38), the median baseline 25 hydroxyvitamin D (25OHD) level was 36.25 (27.5-48.12) nmol/l. After 3 months, 8% of the patients in the control group, 50% in the 125 microg/day group and 75% in the 250 microg/day group had 25OHD values above 85 nmol/l (34 ng/ml). Considering both vitamin D(2) groups together, mmPTH and BAP levels diminished significantly after 3 months (P<0.02), unlike those of CTX. Serum calcium remained within normal range during the follow-up. CONCLUSIONS: The oral dose of vitamin D(2) required to rapidly achieve adequate levels of 25OHD is seemingly much higher than the usual recommended vitamin D(3) dose (20 mug/day). During 3 months, 250 microg/day of vitamin D(2) most effectively raised 25OHD levels to 85 nmol/l in 75% of the postmenopausal osteopenic/osteoporotic women treated.

Bone mineral density in children with celiac disease. Effect of a Gluten-free diet.

OBJECTIVE: To assess the degree of osteopenia in children with celiac disease (CD) at the time of diagnosis and the effect of a gluten-free diet (GFD). DESIGN: Longitudinal and prospective study. SUBJECTS: In total, 24 children (18 girls, six boys) diagnosed with CD by means of an intestinal biopsy were included in the study. Mean+/-s.d. age was 4.9+/-4.3 years. In all, 16 patients were under (2.20+/-0.82 year) and eight were over the age of 4 years (10.30+/-2.90 year). The time between the first symptoms and diagnosis was 17.30+/-24.70 months (range: 2-109 months). Spine bone mineral content (BMC), area and bone mineral density (BMD) were measured by DXA at baseline and 1.17+/-0.93 years after GFD. RESULTS: Before treatment, mean+/-s.d. BMD was 0.46+/-0.13 g/cm(2), the BMD Z-score was -1.36+/-1.20, and was below -1 s.d. in 14 patients (58%). BMC, area and BMD increased significantly on GFD. BMD increased from 0.46+/-0.13 to 0.55+/-0.13 g/cm(2) (P<0.001). BMD Z-score improved from -1.36+/-1.20 to -0.23+/-1.20 after GFD. However, BMD increased more than 1 s.d. in 15 of the 16 children under the age of 4 years, a similar increase was only observed in four of the eight children aged more than 4 years, some of whom did not follow GFD strictly. Height and weight increased significantly with GFD (P<0.001) and the increase correlated positively with the increase in BMD. CONCLUSIONS: Axial BMD below -1 s.d. was found in 58% of children with celiac disease. Axial bone mass reverted to normal values in most children under the age of 4, who had low bone mass, all of whom followed GFD strictly.

Short-term therapy with oral olpadronate in active Paget's disease of bone.

One of the aims of the treatment of Paget's disease with bisphosphonates should be the normalization of the activity of the disease with the shortest possible exposure to the drug. Olpadronate (OPD) is a new bisphosphonate characterized by the dimethylation of the amino group, its potency is near to alendronate, and more soluble in the digestive media than other aminobisphosphonates. We treated 46 patients (28 men and 18 women, mean age 70 years) with active Paget's disease with oral OPD, 200 mg/day for 12 +/- 2 days, except 2 patients who received 400 mg/day. Eight patients had never been treated before, and 38 had previously received antiosteolytic drugs. The period without treatment prior to OPD was (X +/- 1 SD) 14 +/- 12 months. Baseline bone alkaline phosphatase (BALP) (levels fell from (X +/- 1 SD) 54.0 +/- 62.7 IU/ml (range 22-396) to a lowest mean value of 16.2 +/- 6.4 IU/ml (range 8-45) (normal range 5-21 IU/ml). Forty patients normalized BALP values, in most of the cases within the first 3 months after OPD treatment. Two patients showed partial response (> 50% decrease from baseline), three patients presented poor response (< 50% decrease from baseline), and one patient did not respond at all. Two patients complained of gastric discomfort, and one patient had diarrhea, which disappeared after discontinuation of the drug. Follow-up was carried out on 36 patients; 22 patients are still in remission, with an average length of 9.0 +/- 2.6 months. Fourteen patients experienced relapse after 9 +/- 2 months remission. In conclusion, a 12-day treatment with 200 mg/day of OPD proved to be a very effective and well tolerated therapy of Paget's disease and induced biochemical remissions in the vast majority of patients, even in those with very active disease.

Intravenous aminopropylidene bisphosphonate (APD) in the treatment of Paget's bone disease.

We studied the effect of the intravenous administration of the bisphosphonate APD in 9 patients with Paget's bone disease. The medication was given in a daily dose of 25 mg for 7 days in 0.9% saline infusion over 2 hours. At the end of treatment a significant fall of serum calcium and phosphate was observed. The urinary excretion of calcium decreased markedly and the serum levels of the mid-molecule PTH fragment increased from (mean +/- SE) 85 +/- 11 to 122 +/- 16 pg/ml (p less than 0.05). A marked and rapid decline in the hydroxyprolinuria was observed from 297 +/- 61 mg/24 h to 194 +/- 51 mg/24 h (p less than 0.01); meanwhile the serum alkaline phosphatase decreased from 102 +/- 22 to 84 +/- 21 KAU (p less than 0.05). The effect of ADP on suppression of hydroxyprolinuria varied markedly from +1 to -81% and was negatively related to the basal hydroxyprolinuria (r = -0.90; p less than 0.001). The duration of the bone turnover suppression was short. A relapse greater than 30% in hydroxyprolinuria was observed in 6 of 8 patients 2 to 3 months after APD withdrawal. The short-term intravenous administration of ADP is a useful means to rapidly suppress the activity of Paget's bone disease. However, further studies should determine the optimum dose, the length of treatment, and the need to associate oral therapy to induce a prolonged remission.

Normalization of spine densitometry.

We investigated several transformations of bone mineral content (BMC) and area density (BMD), in particular volumetric density (BMAD), to ascertain the influence on (1) body size dependence, (2) diagnostic sensitivity, and (3) precision. These transformations were examined in a group of 657 normal postmenopausal women and 327 women with osteoporotic fracture. First, expression of results as BMAD removed some of the slight dependence on body size; 21% of the variation in BMC and 15% of the variation i BMD were associated with body weight, but only 8% with BMAD. Second, the Z scores compared with those for age-matched controls for BMD and BMC were -1.85 and -1.71, respectively; the Z score for BMAD was -1.64. Third, the precision error for BMC was reduced by expressing results as BMD (1.1 versus 0.5%); BMAD degraded precision slightly (0.7%). BMD appeared to be the optimal expression for bone densitometry because it provided the best diagnostic sensitivity and lowest precision error; there was a minimal influence of body size on BMD results. This study also showed that osteoporotic women, even in the first postmenopausal decade, had low spine BMD, small vertebral area, and low body weight. Such women may be particularly at risk of crush fracture.

Solar ultraviolet B radiation and photoproduction of vitamin D3 in central and southern areas of Argentina.

The incidence of nutritional rickets in the southern part of Argentina is 8-12 times higher than in the rest of the country. Winter 25(OH)D serum levels in normal population of southern areas are lower than in central and northern areas. To elucidate these differences, we compared the photoconversion of provitamin D3 (7-DHC) to previtamin D3 in two cities: Ushuaia (latitude 55 degrees S) and Buenos Aires (34 degrees S). Ampules containing 7-DHC were exposed to sunlight one day in the middle of each month either from 10:30 a.m. to 2:30 p.m. or from 8:00 a.m. to 5:00 p.m. The percentages of photoproducts formed were determined by high performance liquid chromatography (HPLC). Previous studies have proved that this is a valid model to assess "in vitro" the photoproduction of vitamin D3 in human skin. Previtamin D3 + vitamin D3 formed in Ushuaia were less (p < 0.02) than those found in Buenos Aires during all seasons: summer, (X +/- SEM) 6.4 +/- 0.8% vs. 13.2 +/- 1.8%; autumn, 1.2 +/- 0.7% vs. 6.3 +/- 1.3%; winter, 0.8 +/- 0.7% vs. 3.6 +/- 0.7%; spring, 3.4 +/- 0.5% vs. 9.1 +/- 1.1%. The photoproducts produced from 10:30 a.m. to 2:30 p.m. were similar for each month and latitude to those formed when the ampules were exposed from 8:00 a.m. to 5:00 p.m. We conclude that in Ushuaia there is a prolonged "vitamin D winter" during which cutaneous synthesis of vitamin D is absent, leading to lower serum values of 25(OH)D and contributing to the higher incidence of rickets.

Early skeletal effect of alkali therapy upon the osteomalacia of renal tubular acidosis.

The administration of alkaline agents to a 16-year-old girl with severe renal tubular acidosis and osteomalacia caused an almost immediate rise of the urinary excretion of total hydroxyproline. The increment of the dyalizable fraction predominated over the nondyalizable component. Gradually serum phosphate and serum alkaline phosphatase increased whereas urinary calcium and magnesium and phosphate clearance declined. Serum PTH remained elevated throughout. We suggest that the correction of the metabolic acidosis might increase the transport of phosphate and calcium across the functional bone membrane leading to a rapid deposition of lime salts in the uncalcified matrix with a concomitant increase in bone collagen turnover.

Calcium phosphate metabolism and bone disease in patients with homozygous thalassemia.

Calcium and phosphate metabolism were studied in 22 patients with homozygous thalassemia. The overall results showed no significant difference for serum calcium, phosphorus, alkaline phosphatase, immunoreactive parathyroid hormone, or 25-hydroxyvitamin D between thalassemic and control children. However, during the winter, serum 25-hydroxycholecalciferol levels were very significantly decreased in thalassemic children. A study of the hands showed thin metacarpal cortices related to increased resorption. Histomorphometric study of four iliac bone biopsies showed normal osteoclastic resorption and decreased bone formation. Prussian blue staining and x-ray electron microprobe analysis showed iron deposits inside the bone. Whether this finding is critical in the pathogenesis of the bone disease in unknown.

Efficacy of the bisphosphonate APD in the control of Paget's bone disease.

Fifty-four patients with Paget's bone disease have been treated with the bisphosphonate APD. Twenty-six patients had not previously received treatment for Paget's disease; and 28 had been treated before with EHDP alone or in combination with calcitonin. APD was given orally in a mean dose of 500 mg daily (congruent to 6.8 mg/kg of body weight) for 4 to 12 months. Bone pain diminished or disappeared in 34 of 39 patients with symptoms. A very significant diminution of the biochemical indices of bone turnover was observed in all patients, but the responses were faster in patients who had not previously received treatment for Paget's disease. After 4 months of treatment the serum levels of alkaline phosphatase of previously untreated patients diminished from 58.8 +/- 8.0 to 20.0 +/- 3.9 KA units (P less than 0.001) and urinary excretion of hydroxyproline diminished from 108.6 +/- 16.9 to 42.4 +/- 8.3 mg/24 h (P less than 0.001). In 23 of 26 previously untreated patients the biochemical indices decreased to the normal range (complete response). A reduction of 50% or more without reaching the normal range was observed in the other 3 patients (partial response). Actuarial analysis of the duration of the effect 12 months after stopping APD disclosed that 63% of patients who had achieved a complete response but only 23% of those with a partial response were in biochemical remission. A second course of APD was administered to 11 patients. The results were as effective during the second as the first course in 9 patients, whereas 2 patients had no response to retreatment.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of olpadronate in ovariectomized thyroxine-treated rats.

Hyperthyroidism increases bone turnover and induces bone loss. This study examines the effect of thyroid hormone excess on two biochemical markers of bone turnover (hydroxyproline and bone alkaline phosphatase) as well as on bone mineral content (BMC) and bone mineral density (BMD). The possible protective role of dimethyl-APD (olpadronate, OLP), on both suppression of bone turnover and bone mineral loss in ovariectomized (ovx) rats, was also studied. Female Sprague-Dawley rats, were assigned to five groups of eight rats each: sham, ovx, ovx OLP treated (0.3 mg/kg per week), ovx T4 treated (250 micrograms/kg per day), and ovx T4-OLP rats. Rats were killed after 5 weeks of treatment. At the end of the study, blood samples were analyzed for serum calcium, phosphorus, T4, total and bone alkaline phosphatase (ALP and b-ALP), and urinary samples for hydroxyproline/creatinine ratio (HOProl/creat). Moreover, total BMC, BMD, and scanned area were determined by DXA. Ovx T4-OLP-treated rats presented higher values of b-ALP than ovx T4-treated, ovx, and sham rats (p < 0.05). Ovx increased HOProl/creat excretion compared with sham (p < 0.05), but it was similar compared with ovx T4-treated rats. OLP treatment reduced HOProl/creat excretion in both ovx T4-treated (p < 0.05) and ovx rats (p < 0.05). The final BMC in ovx was lower than in the sham group, but the difference was not statistically significant (p < 0.08). The lowest BMC was observed in ovx T4 rats (p < 0.05). When final BMC was expressed per body weight (BMC/W), ovx rats presented a significantly lower BMC/W than sham rats (p < 0.05). Ovx OLP rats had BMC/W levels higher than ovx (p < 0.005), ovx T4 (p < 0.01), and ovx T4-OLP rats (p < 0.01). The ovx group had a final BMD lower than sham animals (p < 0.05), but not significantly different than the ovx T4 rats. BMC and BMD of OLP ovx rats, whether they received T4 or not, was similar to the sham group. The highest final BMD was observed in the ovx T4-OLP group. In summary, the prevention of an increase in HOProl excretion accompanied by the fact that final BMD and BMC in OLP-treated animals were comparable to sham control rats may reflect that OLP administration could inhibit bone resorption in both T4-treated or -untreated rats. Although further studies are necessary, these findings may have clinical relevance in estrogen-depleted patients to whom medical management other than the reduction of T4 administration would be desirable.

Bone mass changes during pregnancy and lactation in the rat.

We examined bone mass changes in the total, axial, and appendicular skeleton as well as in the different subareas of femur and tibia in rats fed on a normal calcium diet. A total of 16 virgin Wistar rats, approximately 5 months of age (270+/-30 g), were assigned to two groups of eight rats each. One group was mated and, for each pregnant rat, a nonpregnant control rat was studied simultaneously. Weaning was performed when the pups reached 38+/-3 g body weight. At the beginning (t = 0), on the first day postpartum (t = 22 days), and at weaning (t = 45 days), total skeleton bone mineral content (BMC), area, and bone mineral density (BMD) were determined by dual-energy X-ray absorptiometry (DXA) in vivo under anesthesia. Body weight increased significantly during pregnancy (p < 0.05) and decreased at weaning, whereas control rats showed a slow, gradual increment without reaching a significant difference. During pregnancy, BMC and area of the total skeleton increased significantly in pregnant rats, but the changes in BMD were not different compared with the control group. A completely different pattern was observed between groups during the 23 days of lactation. While the skeleton continued to grow in the control group (BMC and area increased), the total skeleton of lactating rats showed no change in area (size), small decreases in BMC, and a significant decrease in BMD (p < 0.05). Consequently, although BMC and BMD of both groups were similar at the time of delivery, BMC was 12.0% lower and BMD 4.9% lower at the end of lactation in the lactating rats compared with the control group. The contribution of the maternal skeleton to the lactation period was not similar; that is, the areas with the highest trabecular component showed the greater average differences in BMD at the time of weaning (proximal tibia -19.9%, distal femur -12.6%, spine -10.9%) (p < 0.05), compared with relatively minor, nonsignificant losses in areas where cortical bone predominates (distal tibia -5%, middle tibia -5.2%). Our experimental results demonstrated the usefulness of DXA in vivo to visualize changes in BMD during the reproductive cycle of the rat. Moreover, the data confirm that normal pregnancy in the rat appears to exert little influence on bone, whereas lactation induces significant bone loss, mainly in the areas of predominant trabecular bone.

Body composition and bone mineral density in untreated and treated patients with celiac disease.

Body composition and bone mineral density (BMD) were studied by X-ray absorptiometry in 20 untreated and 12 treated women with celiac disease, as well as in 85 age-matched control women. Untreated patients had a significantly lower body weight, fat mass, lean tissue mass and BMD at the lumbar spine and total skeleton compared to controls (p < 0.001 for all parameters). Treated patients had also a significantly lower body weight (p < 0.01) fat mass (p < 0.05) and bone mineral density at lumbar spine and total skeleton (p < 0.05) compared with controls, but lean tissue mass was not diminished. However, treated patients had a significantly higher body weight, fat mass and BMD of the total skeleton compared with untreated celiac patients (p < 0.01 for all parameters). Serum alkaline phosphatase levels were increased in untreated patients but serum 250HD was normal. In conclusion, celiac disease causes a global and almost universal reduction of fat mass and BMD. The results of this cross-sectional study suggest that osteopenia does not seem to be completely restored by adequate treatment. Alteration of vitamin D metabolism was not the cause of osteopenia in the majority of patients.

Congenital erythropoietic porphyria: skeletal manifestations and effect of pamidronate treatment.

Congenital erythropoietic porphyria (CEP) is a rare disorder of heme biosynthesis. Skeletal abnormalities have been described in patients with this disease. We report a 25-year-old woman with osteodystrophy from CEP. On examination, mild hepatosplenomegaly, multiple hyperpigmented scars, hypertrichosis, erythrodontia and red coloration of urine were found. Biochemical studies showed increased serum levels of alkaline phosphatase, fasting and total 24-h urinary calcium excretion. Serum 250H vitamin-D concentration was low due to avoidance of sun exposure. Skeletal radiographs disclosed marked vertical and horizontal trabecular pattern and biconcavity of most of the dorsal and lumbar vertebral bodies. Several round sclerotic lesions (1-3 cm in diameter) were seen in the skull, pelvis and one lumbar vertebrae. The sclerotic lesions were augmented in size and number compared to X-rays obtained 8 years before. Bone mineral density (evaluated by DEXA) was markedly reduced at the spine and moderately diminished at the proximal femur and total skeleton. Treatment for 11 months with pamidronate (and the addition of hydrochlorotiazide for the last 6 months) reduced to normal values the serum levels of alkaline phosphatase and fasting urinary calcium. The 24-h urinary excretion of calcium and hydroxyproline were also decreased. The BMD increased in all the skeletal areas with presumably hyperactive bone marrow: spine, head, ribs and pelvis (and total skeleton), but did not change at the extremities and diminished at the femoral neck. Patients with CEP may present osteodystrophy characterized by sclerotic lesions and osteopenia, most likely due to accelerated bone turnover in areas of active bone marrow.(ABSTRACT TRUNCATED AT 250 WORDS)

Are the etiologies of cervical and trochanteric hip fractures different?

Review of results published in the past few years indicates that there are several differences between women sustaining trochanteric fractures of cervical hip fractures. In most series women with trochanteric fractures are older, shorter, and lighter than those with cervical fractures. The bone mineral density was found to be lower in trochanteric fractures, but although in the majority of the studies the diminution was statistically significant at the level of the trochanter and spine--with predominant trabecular bone--the decrease was not uniformly significant at the level of the femoral neck or total skeleton. Previous vertebral fractures were twice as common in patients with trochanteric fractures. Ultrasound exploration of the calcaneus disclosed that the values were significantly lower in women with trochanteric fractures and this finding was independent of the diminution of the bone mineral density. On the other hand, fall biomechanics have not been found to be different in the two types of hip fractures. In summary, women with trochanteric fractures have a more severe and generalized bone loss, especially of the trabecular component. Cervical fractures seem to be more related to pelvic structure-failure of the outer diameter of the femoral neck to expand with age and increased acetabular bone width-added to a focal bone loss. The two main types of fractures should be treated separately in epidemiological or clinical studies to increase the knowledge and the possibilities of preventing hip fractures.

Clinical utility of bone mass measurements in adults: consensus of an international panel. The Society for Clinical Densitometry.

Low bone mass predicts future fracture risk as well as high cholesterol or high blood pressure can predict the risk of heart disease or stroke. Prevention of the first fracture should be a clinical goal. In patients without fractures, osteopenia and osteoporosis can be diagnosed based on the extent of reduction in bone mass below mean peak bone mass of young healthy individuals. As bone mass decreases, fracture risk increases exponentially. Clinical situations in which an assessment of bone mass and fracture risk affects therapeutic decisions include estrogen deficiency, vertebral abnormalities, radiographic osteopenia, asymptomatic primary hyperparathyroidism, and long-term corticosteroid therapy. Serial measurements can also be used to monitor the effects of osteoporosis treatments. The appropriate technique and skeletal site for bone mass measurements should be chosen based on the patient's circumstances and the precision of measurement. A clinical interpretation can enhance the value of computer-generated bone mass measurement reports and improve decision making.

Long-term effect of gluten restriction on bone mineral density of patients with coeliac disease.

AIM: To assess the long-term effect of a gluten-free diet on bone mineral density of adults with untreated coeliac disease. METHODS: Bone mineral density was assessed at baseline and after a mean duration of 37 months of treatment in 25 unselected newly diagnosed coeliac patients. RESULTS: At baseline, osteopenia (> -1 s.d. below normal) was evident in the lumbar spine and total skeleton in 18 (72%) and 21 (84%) patients, respectively. At the end of the study, bone density had increased (mean bone mass Z-score increase: Z-score +1.0 for the lumbar spine and +1.1 for total skeleton) in 22 and 23 patients, respectively. Patients who adhered to strict gluten restriction (n = 15) demonstrated a similar bone remineralization in the spine than those patients with partial compliance (n = 10) (mean Z-score increase: +1.0, in both areas). A greater mean annual change in Z-score in the total skeleton was noted in patients who followed strict gluten restriction (0.4 +/- 0.1) respect to those with partial compliance (0.3 +/- 0.1); however, this difference was not statistically significant. Pre-menopausal women had significantly greater remineralization that post-menopausals (P > 0.05). Remineralization showed an inverse correlation with the degree of basal osteopenia (r = -0.525; P < 0.002). CONCLUSIONS: Long-term treatment with gluten-free diet produces a significant improvement in bone density in coeliac patients. Remineralization was more pronounced in patients who better comply with gluten-free diet, in pre-menopausal women and in patients with the lowest baseline bone mineral density.