Is it necessary to screen for celiac disease in postmenopausal osteoporotic women?

Decreased bone mass is a frequent finding in celiac patients, and subclinical celiac disease (CD) appears to be unusually overrepresented among patients with idiopathic osteoporosis. Since silent CD may be more common than previously believed, it has been suggested that all osteoporotic patients should be checked for occult CD. The aim of this study was to explore the prevalence of CD in a well-defined population of postmenopausal osteoporotic women. We evaluated 127 consecutive postmenopausal patients (mean age: 68 years; range: 50-82 years) with verified osteoporosis. The observed prevalence of CD in this group was compared to that observed in a group of 747 women recruited for a population-based study. The screening algorithm used to diagnose CD was based on a 3-level screening using type IgA and IgG antigliadin antibodies (AGA) in all the patients (1st level) followed by antiendomysial antibodies (EmA) and total IgA (2nd level) of samples testing positive, and intestinal biopsy of positive cases (3rd level). At the end of the serological screening, only 1 of 127 osteoporotic women was eligible for jejunal biopsy showing a characteristic celiac flat mucosa (prevalence 7.9 x 1,000; 95% CI 0.2-43.1). In addition, CD was diagnosed in 6 of 747 women of the population-based study (prevalence: 8.0 x 1,000; 95% CI 3.3-18.3). There was no significant difference between the two groups. Therefore, our study showed that the prevalence of CD in postmenopausal osteoporotic women was lower than that reported in previous studies and similar to that of the general population. In conclusion, although the relatively small size of the group tested does not allow us to be conclusive, the results suggest that a case finding policy in postmenopausal osteoporosis would have a high cost/benefit ratio except for patients not responding to conventional therapies, or presenting borderline laboratory results.

Utilidad clínica de los marcadores de formación y resorción ósea / Clinical utility of biochemical merkers of bone turnover

Se evaluó el recambio óseo en distintas situaciones fisiológicas y patológicas que alteran el metabolismo óseo. A tal fin se analizó la utilidad de un marcador bioquímico de formación como la fosfatasa alcalina ósea (FAO) y uno de resorción ósea, como la fracción carboxilo terminal del telopéptido del colágeno tipo I (CTX). En la población adulta normal los hombres y mujeres premenopáusicas no presentaron diferencias significativas. Contrariamente, las mujeres posmenopáusicas tuvieron niveles de FAO y CTX significativamente mayores que éstos dos grupos (p<0,01). Entre el segundo y tercer trimestre de embarazo ambos marcadores aumentaron significativamente (FAO: p<0,009 y CTX: p<0,0003). Mientras la FAO no varió en posmenopáusicas ante el tratamiento hormonal de reemplazo (THR), el CTX disminuyó significativamente (p<0,001). Mujeres posmenopáusicas osteopénicas y osteoporóticas presentaron niveles de CTX y FAO significativamente menores luego de THR o tratamiento con bifosfonatos respecto de las no tratadas (FAO: p<0,05 y 0,03 y CTX: p<0,02 y 0,0001 respectivamente). Pacientes con insuficiencia renal en hemodiálisis presentaron niveles séricos de FAO y CTX significativamente mayores que los controles sanos por edad y sexo (p<0,05). Pacientes hipertiroideos, pagéticos o con patología ósea secundaria a enfermedad celíaca disminuyeron los niveles de FAO y CTX en forma significativa (p<0,05) luego del tratamiento específico. Como se esperaba, el marcador de resorción respondió más rápidamente a cambios en el remodelamiento óseo. Si le sumamos la alta especificidad y sensibilidad del CTX, se sugiere que éste marcador sería de utilidad en todas aquellas patologías en que se sospeche alteración o se quiera determinar el grado del remodelamiento óseo (AU)

Utilidad clínica de los marcadores de formación y resorción ósea / Clinical utility of biochemical merkers of bone turnover

Se evaluó el recambio óseo en distintas situaciones fisiológicas y patológicas que alteran el metabolismo óseo. A tal fin se analizó la utilidad de un marcador bioquímico de formación como la fosfatasa alcalina ósea (FAO) y uno de resorción ósea, como la fracción carboxilo terminal del telopéptido del colágeno tipo I (CTX). En la población adulta normal los hombres y mujeres premenopáusicas no presentaron diferencias significativas. Contrariamente, las mujeres posmenopáusicas tuvieron niveles de FAO y CTX significativamente mayores que éstos dos grupos (p<0,01). Entre el segundo y tercer trimestre de embarazo ambos marcadores aumentaron significativamente (FAO: p<0,009 y CTX: p<0,0003). Mientras la FAO no varió en posmenopáusicas ante el tratamiento hormonal de reemplazo (THR), el CTX disminuyó significativamente (p<0,001). Mujeres posmenopáusicas osteopénicas y osteoporóticas presentaron niveles de CTX y FAO significativamente menores luego de THR o tratamiento con bifosfonatos respecto de las no tratadas (FAO: p<0,05 y 0,03 y CTX: p<0,02 y 0,0001 respectivamente). Pacientes con insuficiencia renal en hemodiálisis presentaron niveles séricos de FAO y CTX significativamente mayores que los controles sanos por edad y sexo (p<0,05). Pacientes hipertiroideos, pagéticos o con patología ósea secundaria a enfermedad celíaca disminuyeron los niveles de FAO y CTX en forma significativa (p<0,05) luego del tratamiento específico. Como se esperaba, el marcador de resorción respondió más rápidamente a cambios en el remodelamiento óseo. Si le sumamos la alta especificidad y sensibilidad del CTX, se sugiere que éste marcador sería de utilidad en todas aquellas patologías en que se sospeche alteración o se quiera determinar el grado del remodelamiento óseo

European origin of patients with Paget's disease of bone in the Buenos Aires area.

Paget's bone disease is heterogeneously distributed and several foci of high prevalence have been reported in Europe, United States, Argentina and Australia. The aim of the present work was to determine the ethnic origin of the disease in Buenos Aires using a cross sectional epidemiological study. Sample choice was based on a sampling according to grandparents' nationality. Ninety five percent of Paget patients were of European descent and 5% were non-European, while in the control group the proportion of European descendants is lower: 83% (OR: 3.7; p < 0.007; IC 95%: 1.4-9.7). Within the group of patients with Paget's disease the proportion of Italian and Russian descendants was higher than expected according to the 1914 Argentinean census. The prevalence of Paget's disease among European migrants was higher than in the control group of citizens. Regardless of environmental factors, it is likely that the migrants carried a higher risk of developing the disease.

Do different aminobisphosphonates have similar preventive effect on experimental thyroid hormone-induced osteopenia in rats?

We compared similar doses of three different aminobisphosphonates (BP): olpadronate (OPD), pamidronate (APD), and alendronate (ALE) on osteopenia induced by thyroxine (T4)-treatment in OVX and SHAM adult rats. Female Sprague Dawley rats (259 +/- 8 g) were treated with vehicle (SHAM+Vh and OVX+Vh), 250 microg T4/kg/day (SHAM+T4 and OVX+T4), 0.3 mg OPD/kg/day (SHAM+OPD and OVX+OPD), 0.2 mg ALE/kg/day (SHAM+ALE and OVX+ALE), 1.5 mg APD/kg/day (SHAM+APD and OVX+APD), T4+OPD (SHAM+T4+OPD and OVX+T4+OPD), T4+ALE (SHAM+T4+ALE and OVX+T4+ALE), and T4 +APD (SHAM+T4+APD and OVX+T4+APD) during a 5-week period. At the onset and at the end of the experiment, total skeleton bone mineral density (BMD) was assessed in vivo by DXA. Lumbar spine and proximal tibia BMDs were evaluated. T4 treatment to SHAM rats did not modify BGP levels significantly: neither did ovariectomy. T4 treatment to OVX rats significantly increased bone-gla-protein (BGP) levels compared with the other studied groups (P < 0.05). BP treatment reduced BGP levels to values significantly lower than SHAM rats (P < 0.05) and reduced bone alkaline phosphatase in SHAM groups (P < 0.05) but no changes were found in OVX groups. The increased D-Pyr excretion observed in SHAM+T4 rats (P = 0.056), OVX+Vh (P < 0.05), and OVX+T4 group (P < 0.001) compared with the SHAM+Vh rats was prevented by the BP treatment. OVX+Vh rats had total skeleton and proximal tibia BMD, and OVX+T4 group had total skeleton, spine, and proximal tibia BMD significantly lower than the SHAM+Vh group. BP treatment was also found to prevent this reduction. The reduced bone resorption and the prevention of bone loss showed no differences among very close, potentially equivalent doses of the three aminoBPs used. Consequently, treatment with very close similar doses of APD, ODP, and ALE prevented bone resorption and bone changes with the same efficacy.

Differences in bone turnover and skeletal response to thyroid hormone treatment between estrogen-depleted and repleted rats.

This study was undertaken to compare the effect of supraphysiological doses of thyroxine (T4) on bone metabolism in SHAM and OVX young adult rats. Female Sprague Dawley rats (220 +/- 2 g, approx. 5 months of age) were divided into four groups of eight animals each. The animals were intraperitoneally injected 6 days per week with vehicle (Vh): 0.001 N NaOH/0.9% NaCl (SHAM+Vh and OVX+Vh) or 250 microg of thyroxine/kg/day (SHAM+T4 and OVX+T4) during a 5-week period. Serum T4 and osteocalcin (BGP), urinary pyridinolines (Pyr), and creatinine (creat) were determined. At the beginning and at end of the experiment, skeletal bone mineral content (BMC), bone mineral density (BMD), and area (A) of the total skeleton, femur, spine, and whole tibia, as well as proximal, middle, and distal areas of the tibia were assessed by dual X-ray absorptiometry (DXA) in an ultra-high-resolution mode. T4 treatment of the SHAM rats did not induce significant changes in BGP level or Pyr/creat excretion compared with the SHAM+Vh control group. However, these two biochemical bone markers significantly increased due to T4 treatment in OVX rats compared with both OVX+Vh and SHAM+T4 groups (P < 0.05 and P < 0.001, respectively). The OVX+T4 group had a significantly lower DeltaBMD than SHAM+T4 rats in all studied regions (P < 0.05) except for the middle tibia region. OVX+T4 groups presented a significantly lower DeltaBMC and DeltaA compared with SHAM+T4 animals (P < 0.001). OVX+T4 rats significantly impaired the DeltaBMD in the femur (P < 0.01), spine (P < 0.05), whole (P < 0.05) and middle (P < 0.05) tibia whereas T4 treatment of SHAM rats only affected, significantly, the whole (P < 0.05) and the proximal tibia region (P < 0.01). T4 treatment affects bone growth in young adult rats. The effect is significantly greater in the estrogen-depleted than in the estrogen-repleted state. The bone site most adversely affected by T4 treatment depends on the estrogen status. The proximal tibia (principally trabecular bone) was the most affected area in estrogen-repleted rats. Conversely, in OVX rats, the middle tibia (principally cortical bone) presented the greatest decrease in bone density.

Osteomalacia in a patient with severe anorexia nervosa.

A 27-year-old woman with anorexia nervosa since adolescence was referred to our unit for generalized bone pain most severe at the pelvis and an inability to stand. She reported a pelvic fracture diagnosed one year earlier, which had failed to heal. Laboratory tests showed low serum phosphate, normal total serum calcium corrected for serum albumin, and very low urinary calcium excretion. Serum bone alkaline phosphatase and parathyroid hormone levels were elevated, whereas 25-hydroxy-vitamin D was severely decreased. Multiple vertebral and rib fractures were seen on plain radiographs. Radiographic images consistent with osteomalacia were pseudofractures of the left inferior pubic ramus, a bilateral complete fracture of the superior pubic ramus, and a characteristic pseudofracture (Looser zone) in the lateral margin of the right scapula. Vitamin D-deficient osteomalacia with secondary hyperparathyroidism was strongly suspected at this point, but it was decided not to confirm this diagnosis by bone biopsy with histomorphometry and osteoid labeling because of the emotional instability of the patient. Dual-energy X-ray absorptiometry disclosed severe demineralization. After two months on calcium and vitamin D supplements, the bone pain had abated and the patient was able to stand. Serum calcium had increased; serum phosphate, 25-hydroxy-vitamin D, and parathyroid hormone had returned to normal, and the pseudofractures showed evidence of healing. Osteoporosis is a well-known complication of anorexia nervosa. This case shows that osteomalacia can also occur. Vitamin D status should be assessed in patients with long-standing severe anorexia nervosa.

Hyperthyroidism influences ultrasound bone measurement on the Os calcis.

The objective of our study was to compare bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) and quantitative ultrasound (QUS) parameters in women with hyperthyroidism and controls. In this cross-sectional study, QUS parameters and BMD values observed in untreated hyperthyroid patients were compared with data obtained from age-matched controls. Twenty-four women with Graves' disease were studied. Eight patients were postmenopausal. All patients had evidence of thyrotoxicosis as indicated by a raised total serum thyroxine and a suppressed serum thyroid stimulating hormone. BMD of the hip, lumbar spine and whole body, and body composition, were measured by DXA. Ultrasound evaluation on the os calcis was performed with an Achilles device. All measurements were performed before antithyroid therapy. The QUS parameters of BUA, SOS and Stiffness were significantly lower in hyperthyroid patients than in controls. Similar results were observed for the BMD of lumbar spine, femoral neck and total skeleton. Lean tissue and fat mass were also significantly decreased in hyperthyroid patients. In conclusion, these findings suggest that hyperthyroidism affects cortical and trabecular bone equally, as well as bone quality. QUS measurements may be helpful for assessing, using a simple and non-irradiating method, the bone effects of thyrotoxicosis.

[Olpadronate prevents cortical and trabecular bone loss induced by supraphysiological dosis of thyroxine in ovariectomized rats]. / El olpadronato previene la pérdida de hueso cortical y trabecular inducida por dosis suprafisiológicas de tiroxina en ratas ovariectomizadas.

The aim of the present report was to clarify the effect of excess T4 on axial and peripheral bone mineral density (BMD) in estrogen-depleted rats. The protective effect of olpadronate (Olpa) on axial and peripheral bone mass in thyroxine-treated rats was also investigated. Female Sprague-Dawley rats were used: SHAM, OVX + Vh, OVX + Olpa (0.3 mg/kg/week), OVX + T4 (250 micrograms/kg/day) and OVX + T4 + Olpa rats. OVX + Vh group presented a BMD lower than SHAM in the tibia (p < 0.01) but not in femur or lumbar spine; the middle tibia BMD did not change but it was lower at the distal (pns.) and proximal levels (p < 0.003) in OVX + Vh. OVX + T4 rats presented a BMD significantly lower than OVX + Vh rats in total tibia (p < 0.02), femur (p < 0.006) and lumbar spine (p < 0.006). Moreover the BMD was lower in all studied areas of the tibia, but it was statistically significant only at the middle level (p < 0.004). OVX + Olpa rats had a BMD higher than OVX + Vh rats in femur (p < 0.002), lumbar spine (p < 0.0001), total (p < 0.001) and proximal tibia (p < 0.001). Surprisingly, total and proximal tibia BMD values in OVX + Olpa rats presented a BMD significantly higher than OVX + T4 rats in femur (p < 0.001), lumbar spine (p < 0.001), tibia (p < 0.001) and proximal tibia (p < 0.0001). It is important to point out that OVX + T4 + Olpa BMD was significantly higher than in SHAM rats at the lumbar spine, total and proximal tibia (p < 0.01). The present study suggests that although supraphysiological thyroid hormone affected both cortical and trabecular bone, under estrogen-depleted conditions, the cortical bone appears to be more sensitive than the trabecular bone to T4 treatment. We also found that Olpa could prevent the peripheral and axial bone loss induced by thyroid hormone excess.

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.