Bone mineral density and osteoporosis in heart transplanted patients: A single‐center retrospective study at Skåne University Hospital in Lund 1988‐2016

Bone mineral density (BMD) in the lumbar spine and femoral neck, the incidence of osteoporosis, and survival up to 10 years after heart transplantation (HT) were investigated in 169 patients who underwent HT at Skåne University Hospital in Lund, Sweden, 1988‐2016. Within the first year post‐transplantation, mean (SD) BMD decreased by 3.9% (10.1) (P < 0.001) and 9.0% (10.5) (P < 0.001) in the lumbar spine and femoral neck, respectively. The cumulative incidence of osteoporosis in the lumbar spine and femoral neck increased rapidly within the first year after HT and was detected in 17% and 13% of the patients, respectively. A higher T score before HT was a negative predictor of osteoporosis up to 10 years post‐HT in the lumbar spine (HR 0.13; 95% CI 0.063‐0.26; P < 0.001) and femoral neck (HR 0.54; 95% CI 0.34‐0.85; P < 0.001). Moreover, only 13%, 14%, and 6% of the HT patients received calcium, vitamin D, and/or bisphosphonates before HT. In conclusion, BMD drops significantly during the first postoperative year. Optimization of BMD early among HT candidates, potentially through usage of osteoporosis preventive treatment, may be a future means to prevent osteoporosis late postoperatively.     

A Prospective Study of Bone Loss in Menopausal Australian-Born Women

Two hundred and twenty-four women (74 pre-, 90 peri-, 60 post-menopausal), aged 46–59 years, from a population-based cohort participated in a longitudinal study of bone mineral density (BMD). BMD was measured by dual-energy X-ray absorptiometry (DXA) at the lumbar spine and femoral neck and the time between bone scans was on average 25 (range 14–41) months. The aim of the study was to assess changes in BMD in relation to changes in normal menopausal status. During the study period women who were between 3 and 12 months past their last menstrual period (n= 22, late perimenopausal) at the time of the second bone scan had a mean (SE) annual change in BMD of 70.9% (0.4%) at the lumbar spine and 70.7% (0.6%) at the femoral neck (both p50.05 compared with women who remained premenopausal). In the women who became postmenopausal (n= 42) the mean annual changes in BMD were 72.5% (0.2%) at the lumbar spine and 71.7% (0.2%) at the femoral neck (both p50.0005), and in the women who remained postmenopausal (n= 60) they were 70.7% (0.2%) per year and 70.5% (0.3%) per year respectively (both p50.05), compared with women who remained premenopausal. In the 1–3 years after the final menstrual period (FMP) there was greater bone loss from the lumbar spine than the femoral neck (p50.05). In women who were menstruating at the time of the second bone scan and whose FMP could be dated prospectively (n= 35), higher baseline oestradiol levels were associated with less lumbar spine bone loss (p50.005). In the women who remained postmenopausal there was an association between baseline body mass index (BMI) and percentage change per year in femoral neck BMD (p50.05), such that women with higher BMI had less bone loss. In conclusion, during the time of transition from peri- to post-menopause, women had accelerated BMD loss at both the hip and spine. Received: 23 June 1997 / Accepted: 5 November 1997     

Intravenous Pamidronate as Treatment for Osteoporosis after Heart Transplantation: A Prospective Study

Fractures due to osteoporosis are one of the major complications after heart transplantation, occurring mostly during the first 6 months after the graft, with an incidence ranging from 18% to 50% for vertebral fractures. Bone mineral density (BMD) decreases dramatically following the graft, at trabecular sites as well as cortical sites. This is explained by the relatively high doses of glucocorticoids used during the months following the graft, and by a long-term increase of bone turnover which is probably due to cyclosporine. There is some evidence for a beneficial effect on BMD of antiresorptive treatments after heart transplantation. The aim of this study was to assess prospectively the effect on BMD of a 3-year treatment of quarterly infusions of 60 mg of pamidronate, combined with 1 g calcium and 1000 U vitamin D per day, in osteoporotic heart transplant recipients, and that of a treatment with calcium and vitamin D in heart transplant recipients with no osteoporosis. BMD of the lumbar spine and the femoral neck was measured by dual-energy X-ray absorptiometry in all patients every 6 months for 2 years and after 3 years. Seventeen patients, (1 woman, 16 men) aged 46 ± 4 years (mean ± SEM) received only calcium and vitamin D. A significant decrease in BMD was observed after 6 months following the graft, at the lumbar spine (−6.6%) as well as at the femoral neck (−7.8%). After 2 years, BMD tended to recover at the lumbar spine, whereas the loss persisted after 3 years at the femoral neck. Eleven patients (1 woman and 10 men) aged 46 ± 4 years (mean ± SEM) started treatment with pamidronate on average 6 months after the graft, because they had osteoporosis of the lumbar spine and/or femoral neck (BMD T-score below −2.5 SD). Over the whole treatment period, a continuous increase in BMD at the lumbar spine was noticed, reaching 18.3% after 3 years (14.3% compared with the BMD at the time of the graft). BMD at the femoral neck was lowered in the first year by −3.4%, but recovered totally after 3 years of treatment. In conclusion, a 3-year study of treatment with pamidronate given every 3 months to patients with existing osteoporosis led to a significant increase in lumbar spine BMD and prevented loss at the femoral neck. However, since some of these patients were treated up to 14 months after the transplant, they may already have passed through the phase of most rapid bone loss. In patients who were not osteoporotic at baseline, treatment with calcium and vitamin D alone was not able to prevent the rapid bone loss that occurs immediately after transplantation. Received: 31 June 2000 / Accepted: 23 August 2000     

Factors Underlying Changes in Bone Mineral During Postpartum Amenorrhea and Lactation

To determine the physiologic and habitual factors that may modulate changes in bone mineral density (BMD) postpartum, dual-energy X-ray absorptiometry was performed at the lumbar spine, right femoral neck and dominant distal radius immediately after delivery, after resumption of menses, and 1 year thereafter in a cohort of 41 healthy postpartum Finnish women aged 31.5 (SD 4.6) years. Mean durations of lactation and postpartum amenorrhea (PPA) were 7.7 (3.7) and 5.9 (2.9) months, respectively. After PPA, significant bone losses of 2%–4% were observed at the lumbar spine and femoral neck. Duration of PPA and different lactational variables explained (adjusted R ²) from 21% to 27% of the variability in changes in BMD during PPA. A recovery to postpregnancy BMD levels was observed at the lumbar spine; in contrast BMD at the femoral neck showed only a partial recovery. The duration of unsupplemented lactation was weakly (adjusted R ²= 0.13) associated with recovery at the lumbar spine, while a long duration of total lactation also showed a weak association (adjusted R ²= 0.02) with delayed recovery at the femoral neck. In conclusion, a systematic bone loss occurs during PPA, and after resumption of menstruation BMD recovers despite continued lactation. However, the time of bony recovery back to postpregnancy level seems to be modulated slightly by lactation habits. It is obvious that the control of postpartum BMD changes is a multifactorial process that may be specific to the skeletal site of interest. Received: 7 June 1999 / Accepted: 5 January 2000     

The Effect of Low-Dose Cholecalciferol and Calcium Treatment on Posttransplant Bone Loss in Renal Transplant Patients: A Prospective Study

Background/Aim. Posttransplant steroid doses have been reduced with the use of new and potent immunosuppressive agents. However, posttransplant osteoporosis is still a serious problem. Our aim in this study was to investigate the effect of low-dose cholecalciferol and calcium supplementation on bone loss after transplantation in renal transplant patients. Methods. Fifty-eight renal transplantation patients were included in the study. Fourteen newly transplanted patients (group 1) and 44 renal transplantation patients with a graft age of at least six months (group 2) were involved. All patients received 400 IU/day orally cholecalciferol (vitamin D3) and 600 mg/day orally calcium replacement starting from the second day posttransplantion. All patients baseline serum and urine biochemistry, serum 25-hydroxy vitamin D3 (25 (OH)D3), and bone mineral density (BMD) tests were performed. Also, the same measurements were performed at the 12th month in group 1. Results. After one year of treatment, BMDs were improved in group 1. Patients in group 1 had a nonsignificant increase of lumbar spine (8.12 ± 18.64% of baseline BMD) and femoral total (7.10 ± 13.48% of baseline BMD) BMD at the end of the first year. On the other hand, there was a significant increase in femoral neck (10.06 ± 15.70% of baseline BMD, p < 0.05) measurements. The baseline results of group 2 were similar to group 1. In group 1, 25 (OH)D3 levels were increased while PTH levels were decreased at the end of the year. Conclusion. In renal transplant patients who use low-dose metilprednisolon and new immunosuppressive agents together, low doses of vitamin D3 and calcium replacement for one year provides a reduction in lumbar spine, femoral neck, and femoral total bone loss and prevents bone loss in group 2. In addition, it contributed to the normalization of PTH levels.     

Bone mineral density 6 years after a hip fracture: a prospective, longitudinal study

The purpose of this prospective study was to extend the results of previous studies to determine if an accelerated rate of loss of bone mineral density (BMD) continues for 6 years after a hip fracture. Eighty-five elderly patients who had sustained a hip fracture had determinations of BMD made at the time of fracture; 55 of these patients were available for reassessment of BMD 1 year later, and 21 were available for reassessment of BMD 6 to 7 years later. The change in BMD from injury to 1 year and from 1 to 6 years was determined and correlated with pre- and postinjury variables, such as ambulatory ability, dietary intake of calcium, serum vitamin D levels, and mental status. There was a marked decrease in BMD in the in the first year after fracture, with the mean change in BMD being -4.3% at the femoral neck and -1.8% at the lumbar spine. Between 1 and 6 years after fracture, however, there was a dramatic increase in the BMD at both the femoral neck and lumbar spine measurement sites. Relative to 1 year after fracture, the mean increases were 7.7% at the femoral neck and 4.5% at the lumbar spine. In many cases, the loss of bone mineral that occurred in the first year after fracture was completely recouped in the subsequent 5 years. Five of the 21 patients (24%) sustained a contralateral hip fracture in the 6 years after the index fracture. Lumbar spine BMD was lower at baseline (p = 0.112), 1 year after fracture (p = 0.007), and 6 years after fracture (p = 0.003) in patients who sustained a second hip fracture than in those who did not. There was a general decrease in the functional activity level of patients in the 6 years after a hip fracture, but there were no statistically significant relationships between changes in BMD and the functional mobility of patients. The mean calcium intake in patients improved remarkably in the 6 years after fracture, but there was no correlation between daily calcium intake and changes in BMD. During the first year after a hip fracture, there is a rapid loss of bone mineral from the lumbar spine and contralateral femoral neck. Between 1 and 6 years after fracture, however, BMD is likely to increase, perhaps to levels greater than those at baseline. Although this investigation is small, the findings of this study point to the importance of further larger studies to further clarify the natural history of BMD after a hip fracture and the potential impact of pharmacological intervention on that natural history.     

Vitamin D receptor start codon polymorphism (<Emphasis Type="Italic">Fok</Emphasis>I) is related to bone mineral density in healthy adolescent boys

 Peak bone mass is considered a major determinant in the emergence of osteoporosis and is mainly genetically regulated. Several genes have been investigated, among them the vitamin D receptor (VDR) gene. A single-nucleotide polymorphism (defined by the endonuclease FokI) located in the start codon of the VDR creates the alleles F and f, resulting in different proteins. A number of previous studies have proved the F allele to be more advantageous as concerns bone mineral density (BMD). In this longitudinal study of 88 adolescent boys, we have investigated whether the different genotypes are associated with BMD, bone mineral content (BMC), or bone area. BMD, BMC, and bone area of the right femoral neck, lumbar spine, and total body were measured using dual-energy X-ray absorptiometry. Differences in phenotypes in relation to the FokI polymorphism were calculated by means of an analysis of variance (ANOVA), with Bonferroni's correction for multiple comparisons. At the first examination, the FokI genotypes were significantly related to lumbar spine BMC and total body bone area in boys aged 16.9 ± 0.3 years (mean ± SD). There was a strong tendency towards significance as regards pubertal stage, total body and femoral neck BMC, weight, lean body mass, lumbar spine bone area, and lumbar spine BMD. There were no significant differences in height, fat mass, birth height and weight, total body and femoral neck BMD, and femoral neck bone area. Regression analysis proved the FokI genotypes to be independently related to lumbar spine BMD (FF > ff; P < 0.01), and possibly total body BMD (P = 0.06), but not femoral neck BMD. At the second examination, approximately 2 years later, our ANOVA results showed significance as regards femoral neck BMC and weight. Using multiple regression, the FokI genotypes were independently related to lumbar spine BMD (FF > ff; P = 0.03), and total body BMD (P < 0.05), but not femoral neck BMD. This study proves the FokI polymorphism to be an independent predictor of lumbar spine BMD are probably total body BMD, but not femoral neck BMD. Received: December 25, 2001 / Accepted: October 7, 2002 Offprint requests to: M. Lorentzon     

Alendronate decreases the fracture risk in patients with prostate cancer on androgen‐deprivation therapy and with severe osteopenia or osteoporosis

OBJECTIVE

To evaluate changes in bone mass and fracture risk in patients with prostate cancer on androgen‐deprivation therapy (ADT) and with a basal T‐score of >?2.0, who were treated with an oral bisphosphonate, as such patients treated with ADT are at increased risk of bone loss and bone fracture.

PATIENTS AND METHODS

We selected 61 patients with prostate cancer treated with ADT; 31 were treated with oral alendronate 70 mg once‐weekly and a control group of 30 were not. At baseline and 12 months we measured bone mineral density (BMD) of the lumbar spine, femoral neck and total hip by dual‐energy X‐ray absorptiometry. All patients had severe osteopenia or osteoporosis at baseline. The risk of femoral neck fracture was calculated at baseline and 12 months (Z‐score 2.7).

RESULTS

Patients treated with alendronate had a significant increase in BMD at the lumbar spine and femoral neck after 1 year of follow‐up, with mean (sd ) values of 1.06 (0.26) vs 1.01 (0.21) g/cm² at baseline (P < 0.001), and 0.75 (0.07) vs 0.73 (0.07) g/cm² (P = 0.03), respectively, while the control group had a significant loss of BMD at the total hip of 0.79 (0.14) vs 0.81 (0.13) g/cm² (P = 0.03). BMD was significantly improved at the three locations in patients treated with alendronate compared with the control group, with differences at the lumbar spine, femoral neck and total hip of 0.05 (0.07) vs 0.01 (0.10) (P = 0.001), 0.01 (0.04) vs ?0.002 (0.03) (P = 0.04) and 0.01 (0.04) vs ?0.01 (0.02) g/cm², respectively (P = 0.001). Patients treated with alendronate had a significant decrease in the fracture risk at the femoral neck, by ?0.54 (1.29) (P = 0.04) after 1 year of follow‐up.

CONCLUSIONS

Treatment with once‐weekly 70 mg alendronate significantly improved the BMD at the lumbar spine and femoral neck in patients with prostate cancer with severe osteopenia or osteoporosis and on ADT, and significantly decreased the risk of femoral neck fracture.     

Bone mineral density in premenopausal women treated for node-positive early breast cancer with 2 years of goserelin or 6 months of cyclophosphamide,methotrexate and 5-fluorouracil (CMF)

The purpose of this study was to compare changes in bone mineral density (BMD) in premenopausal patients with node-positive early breast cancer treated with goserelin (Zoladex) or cyclophosphamide, methotrexate and 5-fluorouracil (CMF). Patients (n=1640) were randomized to goserelin (3.6 mg every 28 days for 2 years) or CMF (six×28-day cycles) treatment. In a protocoled sub-study involving 96 patients from eight centers (goserelin: n=53; CMF: n=43), lumbar spine (L2–L4) and femoral neck BMD were assessed by dual X-ray absorptiometry at baseline and then annually for 3 years. At the end of the 2-year goserelin-treatment period, mean BMD losses for goserelin-treated and CMF-treated patients were –10.5% and –6.5% (P=0.0005) for lumbar spine and –6.4% and –4.5% (P=0.04) for femoral neck, respectively. At 3 years, partial recovery of BMD was observed in goserelin recipients. In contrast, mean BMD losses for the CMF group indicated persistent BMD loss. No significant differences in BMD were observed between groups at the 3-year assessment of the spine or femoral neck. In the CMF group, based on amenorrhea status at 48 weeks, BMD losses at the lumbar spine were greater for amenorrheic than non-amenorrheic patients. Ovarian suppression resulting in amenorrhea was closely related to BMD loss in both treatment groups. Overall, patients who received CMF did not show recovery of BMD throughout follow-up, whereas partial recovery was observed 1 year after cessation of goserelin therapy, associated with the return of ovarian function in the majority of patients.     

Associations between osteoprotegerin and femoral neck BMD in hemodialysis patients

Numerous humoral factors are involved in the development of renal osteodystrophy, causing perturbations in bone mineral density (BMD) in patients with end-stage renal disease (ESRD). The RANKL/OPG cytokine system appears to mediate the effects of many of these factors on bone turnover, contributing to the pathogenesis of renal bone disease. The aim of this study was to evaluate the clinical and biochemical correlations of BMD measurements in patients on chronic hemodialysis. Fifty-four hemodialysis patients underwent measurement of BMD at the proximal femur and the lumbar spine (L2–L4). Intact parathyroid hormone (PTH), osteoprotegerin (OPG), sRANKL, and main bone biochemical markers were also measured in serum samples of all patients. BMD of the femoral neck was negatively correlated with OPG levels (r = 0.333, P = 0.014). OPG levels were significantly different among normal, osteopenic, and osteoporotic tertiles defined according to BMD of the femoral neck. The highest OPG levels were measured in the lowest T-score (osteoporotic) tertile and were higher than in the osteopenic and normal tertiles (P < 0.05). A threshold level for OPG at 21.5 pmol/l enabled the detection of osteoporotic patients with 76.5% sensitivity and 62.2% specificity. BMD values of trabecular bone-rich sites of the skeleton such as lumbar spine (L2–L4), trochanter, and Ward’ s triangle were inversely correlated with total ALP levels (P < 0.05). Hemodialysis patients with low BMD of the femoral neck demonstrated higher OPG levels than patients with normal BMD. Those with lumbar spine (L2–L4), trochanteric, and Ward's triangle BMDs below the normal range presented higher total ALP levels. These results suggest that OPG and total ALP may be clinically useful markers in the detection of significant femoral neck and trabecular bone mineral deficit in hemodialysis patients, warranting further investigations.     

Risk factors for low bone mineral density and the 6-year rate of bone loss among premenopausal and perimenopausal women

Risk factors that are associated with lower bone mineral density (BMD) may not necessarily be associated with increased bone loss among premenopausal and perimenopausal women. We determined risk factors for lower premenopausal and perimenopausal BMD while simultaneously determining risk factors for increased 6-year rate of bone loss among women aged 24–50 years within a population-based prospective cohort study. BMD of the lumbar spine and femoral neck, reported as t scores, were measured five times within the 6-year study among 614 women who were between the ages of 24 and 44 in 1992/1993. Rates of bone loss were calculated from the repeated BMD measurements. Risk factors for lower BMD over time at the lumbar spine included history of any fracture (P=0.005). The major risk factor for lower BMD over time at the femoral neck was family history of osteoporosis (P<0.002). The major protective factor for greater BMD over time at both skeletal sites was additional body weight (P<0.0001). Other protective factors for greater BMD over time at the femoral neck were modest alcohol consumption (P=0.0002) and high-school sports participation (P=0.002). Risk factors for greater bone loss at either skeletal site included postmenopausal status (P<0.0001 at the lumbar spine; P=0.01 at the femoral neck), and the reporting of a reproductive cancer (P<0.0001 at the lumbar spine; P=0.0008 at the femoral neck). Body weight was protective against bone loss at both skeletal sites (P<0.0001). Baseline age, calcium intake, smoking, and current physical activity were not associated with BMD or bone loss. The understanding of the relative importance of risk factors for both low BMD and bone loss may assist in the identification of women at greater risk for subsequent low postmenopausal BMD.     

Areal and volumetric bone density in Hong Kong Chinese: a comparison with Caucasians living in the United States

It is a common perception that Asians have lower bone density than Caucasians. However, such relationships could be confounded by bone size. In this study, the skeletal status of a convenience sample of 482 men and 887 women living in Hong Kong is compared with published data for Caucasians living in Rochester, Minnesota. Areal bone mineral density (BMD, g/cm²) and volumetric bone mineral apparent density (BMAD, g/cm³) were determined for the lumbar spine and proximal femur, using the Hologic QDR 2000 instrument. Cross-calibration was performed by measuring a common phantom, and the Hong Kong data were adjusted by a multiplication factor. Lumbar spine and femoral neck BMD and BMAD of Chinese men and women were all significantly lower (P<0.001 by t-test) than those of Caucasians, but the differences in BMAD were on average only about half the size of the differences in BMD. For instance, in postmenopausal Chinese women, BMD at the femoral neck and lumbar spine were 15.2% and 18.8% lower respectively, but BMAD at the femoral neck and lumbar spine were only 7.8% and 12.4% lower respectively. Similar trends were observed in men. After adjusting for age, body height and weight, the difference in BMAD between Caucasians and Chinese was further reduced and only statistically significant among postmenopausal women and among men younger than age 50 years for the lumbar spine. For instance, the adjusted BMAD in postmenopausal Chinese women at the femoral neck and lumbar spine were 3.9% (P=0.03 by ANCOVA) and 7.3% (P<0.001 by ANCOVA) lower respectively, while the adjusted BMAD at the lumbar spine for Chinese men younger than 50 years was 11.7% lower (P<0.01 by ANCOVA). Predictors of BMAD in Hong Kong Chinese women include body weight, age at menarche, cigarette smoking, and oral contraceptive use (P<0.001), while body weight was the only independent predictor of BMAD in Hong Kong Chinese men (P<0.001). We conclude that bone density is lower in Hong Kong Chinese men and women than in Caucasians, although such differences were attenuated by adjustments for bone size, body weight and height.     

Femoral and spinal bone mineral density in Japanese osteoporotics with hip fracture

In the present study, bone mineral density (BMD) of femoral neck and lumbar spine was compared between 38 Japanese female patients with hip fracture (age 63–89 years, mean±SD 76±7 years) and 162 age-matched female controls (age 62–90 years, mean±SD 75±7 years). BMD was measured in the femoral neck and lumbar spine (L2–4) using dual-photon absorptiometry (Norland model 2600). BMD values of femoral neck as well as lumbar spine were significantly lower in patients with hip fracture than in controls (0.504±0.097 v 0.597±0.101,p<0.01, for femoral neck; 0.661±0.146 v 0.720±0.128,p<0.05, for lumbar spine). Patients with hip fracture and controls were stratified according to their BMD levels at two measuring sites, and the ratio of the number of patients and controls at each BMD level was calculated as an indicator of fracture rate. This ratio showed an exponential increase as the femoral neck BMD declined, but only a gradual increase as the lumbar spine BMD declined. Specificity-sensitivity analysis revealed that BMD values of 0.59 and 0.54 g/cm² at the femoral neck provided a specificity of 52% and 68% with a sensitivity of 90% and 75%, respectively. These findings suggest that Japanese patients with hip fracture are more osteoporotic than age-matched controls and that the selective measurement of femoral neck would be useful for predicting the risk of hip fracture.     

Bone Loss in Long-Term Survivors after Transplantation of Hematopoietic Stem Cells: A Prospective Study

Organ transplantation is associated with relevant bone loss. Bone loss of up to 20% of pretransplant bone mineral density (BMD) values within the first year after kidney, liver, heart and lung transplantation has been reported. Patients undergoing transplantation of hematopoietic stem cells provide an interesting model to study transplantation-induced bone loss, especially because most patients do not have pre-existing bone disease. A longitudinal study was performed in 81 patients undergoing bone marrow or peripheral blood stem cell transplantation. BMD was determined by dual-energy X-ray absorptiometry before transplantation, at discharge from the hospital, and at 6 and 12 months after transplantation in all 81 patients. In 35 patients BMD was re-evaluated 24 months after transplantation. Vitamin D and parathyroid hormone, bone alkaline phosphatase as a marker of bone formation, and N-terminal telopeptide of type I collagen as a marker of bone resorption were assessed before transplantation and in the short-term follow-up 14 and 28 days after transplantation. The majority of patients (72%) showed normal BMD before transplantation. However, lower BMD was observed in patients who had received high-dose cytoreductive chemotherapy before transplantation compared with those who had received no chemotherapy or only hydroxyurea. Despite supplementation with elemental calcium (1000 mg/day) and vitamin D (1000 IU/day), the mean rate of bone loss during the first year was 7.2 ± 6.3% at the lumbar spine, 11.9 ± 8.1% at the femoral neck and 3.8 ± 2.5% at the total body compartment. Evaluation of the pattern of bone loss during the first year demonstrated that the amount of bone loss was largest within the first 40 days after transplantation and small during the second half of the first year after transplantation. The majority of patients showed vitamin D deficiency and secondary hyperparathyroidism. Bone formation was normal before and after transplantation, whereas bone resorption was dramatically increased before and after transplantation. Exposure to glucocorticoids was associated with higher bone loss at spine and femoral neck but not at the total body compartment. Our data demonstrate rapid bone loss in patients undergoing transplantation of hematopoietic stem cells. Bone turnover is characterized by biochemical uncoupling of bone resorption and bone formation, changes interestingly pre-existing before transplantation. The observed alterations in bone mass and metabolism emphasize the importance of clinical trials with antiresorptive agents to prevent and treat post-transplantation osteoporosis in this group of patients. Received: 30 March 1999 / Accepted: 10 October 1999     

Beneficial treatment with risedronate in long-term survivors after allogeneic stem cell transplantation for hematological malignancies

In this prospective randomized study we evaluated the effect of risedronate, an aminobisphosphonate, on bone mass and turnover in patients who had undergone allogeneic stem cell transplant (SCT) for hematological malignancies. Thirty-four patients (18 females, 16 males, age 32±10 years) with bone mineral density (BMD) –1.5 SD as a T-score at least 6 months after SCT were treated with calcium 1 g/day and vitamin D 800 IU/day and randomized to receive (n=17, group 1) or not receive (n=17, group 2) oral risedronate 5 mg/day. The duration of treatment was 12 months. After 6 months, lumbar BMD increased by 4.4±1.6% in patients of group 1 and decreased by 4.3±1.5% in those of group 2 (P<0.05); at the femoral neck, BMD did not change significantly in patients of group 1 (+1.2±1.2%), while it decreased in those of group 2 (–4.3±2.1%; P<0.05). After 12 months, lumbar BMD further increased (+5.9±1.7%, P<0.05), compared to baseline in group 1 and slightly increased (+1.1±1.4%) in group 2. No further changes were observed at femoral neck in both groups. In conclusion, treatment with risedronate for 12 months increased BMD significantly at the lumbar spine and prevented further bone loss at the femoral neck in long-term survivors after allo-SCT.     

Differential action of pamidronate on trabecular and cortical bone in women with involutional osteoporosis

Since osteoporotic fractures are mainly related to the diminution of the bone mineral density (BMD), the effect of pamidronate (3-amino-1-hydroxy-propylidene) 1,1-bisphosphonate on the BMD of the spine, proximal femur and radius shaft was evaluated in an initial cohort of 35 postmenopausal women with at least one vertebral fracture due to involutional osteoporosis.Pamidronate was given continuously during 18 months in a daily oral dose of 4.8 to 6.0 mg/kg supplemented with calcium (1 g/day).BMD — measured by dual photon absorptiometry — increased after one year 5.3±1.0% (P<0.001) in lumbar spine and 5.3±1.5% (P<0.001) over trochanter. However no significant changes were observed in the BMD of the femoral neck, Ward's triangle or in the cortical bone of the radius shaft measured by single photon absorptiometry.Pamidronate also decreased significantly urinary hydroxyproline-creatinine excretion after 6 months and thereafter maintained a plateau. After 18 months of treatment the diminution was 42.6±4.9% (P<0.001).The differing effects of pamidronate on the BMD of lumbar spine and proximal femur might be ascribed to dissimilarities between the proportions of trabecular and cortical bone in these. These results suggest that pamidronate may be prescribed to prevent fractures in cases of involutional osteoporosis with a significant decrease of BMD in lumbar spine and/or trochanter.     

Urinary N‐telopeptide and Rate of Bone Loss Over the Menopause Transition and Early Postmenopause

The purpose of this study was to assess the ability of urinary N‐telopeptide (U‐NTX) to gauge rate of bone loss across and after the menopause transition (MT). U‐NTX measurement was measured in early postmenopause in 604 participants from the Study of Women's Health Across the Nation (SWAN). We examined the association between U‐NTX and annualized rates of decline in lumbar spine and femoral neck bone mineral density (BMD) across the MT (1 year before the final menstrual period [FMP] to time of U‐NTX measurement), after the MT (from time of U‐NTX measurement to 2 to 4 years later), and over the combined period (from 1 year before FMP to 2 to 4 years after U‐NTX measurement). Adjusted for covariates in multivariable linear regression, every standard deviation (SD) increase in U‐NTX was associated with 0.6% and 0.4% per year faster declines in lumbar spine and femoral neck BMD across the MT; and 0.3% (lumbar spine) and 0.2% (femoral neck) per year faster declines over the combined period (across and after the MT) (all p < 0.01). Each SD increase in U‐NTX was also associated with 44% and 50% greater risk of fast bone loss in the lumbar spine (defined as BMD decline in the fastest 16% of the distribution) across the MT (p < 0.001, c‐statistic = 0.80) and over the combined period (across and after the MT) (p = 0.001, c‐statistic = 0.80), respectively. U‐NTX measured in early postmenopause is most strongly associated with rates of bone loss across the MT, and may aid early identification of women who have experienced fast bone loss during this critical period. © 2016 American Society for Bone and Mineral Research.     

Identification of Women with Reduced Bone Density at the Lumbar Spine and Femoral Neck using BMD at the Os Calcis

We assessed the clinical usefulness of bone density measurements at the os calcis as a screening tool to identify patients with low bone density at the lumbar spine and femoral neck. Bone mineral density (BMD) was recorded in 443 women (mean age 60 years) referred to a bone densitometry service. Measurements were made at the lumbar spine and femoral neck using a Lunar DPXL and at the right os calcis using a Peripheral Instantaneous X-ray Imaging (PIXI) dual-energy X-ray absorptiometry system. Average T-scores derived using the manufacturer”s data were: 1.59 for the lumbar spine, −1.41 for the femoral neck and −0.87 for the os calcis. The prevalence of osteoporosis using WHO criteria (T-scores of −2.5 or less) was 36% for the lumbar spine or femoral neck but only 9.7% for the os calcis. BMD of the os calcis correlated with that at the lumbar spine (r= 0.69, p<0.001) and femoral neck (r= 0.67, p<0.001). The area under the receiver operator characteristics curve was 0.836 (standard error 0.020) for the os calcis related to osteoporosis at the lumbar spine or femoral neck. Optimal accuracy was obtained at a T-score of ≤−1.3 (BMD 0.39 g/cm²) when the sensitivity was 69.6% (95% confidence interval 65.3, 73.9%) and specificity 82.6% (95% confidence interval 79.1, 86.1%). However, the probability of diagnosing low bone density from a given BMD at the os calcis varied by age and site scanned. Accordingly, for informing management strategies, the choice of a single cutoff BMD at the os calcis may not be appropriate and several thresholds may be adopted based on age, the site of interest (lumbar spine or femoral neck) and consideration of associated clinical features. Thus, the use of heel bone density scanners could reduce the number of axial bone density measurements required. The advantages of portability, low cost and shorter scan times should reduce the cost of detection and provide a greater opportunity for identification of women at risk of fracture. Received: 18 June 1999 / Accepted: 30 March 2000     

骨密度在髋部骨质疏松性骨折风险评估中的价值

目的评估骨密度在髋部脆性骨折风险预测中的临床价值。方法回顾性研究2014年6月至2019年6月在我院创伤骨科住院的老年髋部骨折患者72例,作为病例组,其中股骨转子间骨折31例,股骨颈骨折41例;对照组选择同期我院骨外科门诊老年体检者63例。使用DXA方法测量患者腰椎和健侧髋部(全髋部、转子间、股骨颈、Ward’s区)的骨密度;对照组测量腰椎和左侧髋部骨密度,统计分析测量结果。结果①骨折组腰椎、髋部骨密度均显著低于对照组,差异有统计学意义(P0.01);②转子间骨折组和股骨颈骨折组在腰椎和髋部区域骨密度比较差异均无统计学意义(P 0.05);③骨折组与对照组在转子间区的T值降低比例最大为122.1%,腰椎降低幅度最小为31.3%,余髋部的T值均有不同程度降低;④骨折后髋部和腰椎T值比存在倒置现象;⑤对照组和骨折组髋部骨质疏松程度比较,差异有统计学意义(P0.01);两组患者腰椎骨质疏松程度比较,差异无统计学意义(P0.05)。结论①髋部骨折患者骨密度均显著低于体检者,提示骨密度与髋部骨折具有一定相关性,但与髋部骨折类型无关;②在髋部骨折风险评估中,髋部骨密度相比腰椎更有价值;③当髋部与腰椎T值比出现倒置时,将不可避免发生髋部骨折;④骨量正常的部分患者发生了脆性骨折,而骨质疏松的部分患者却未发生骨折,表明影响骨折发生的因素除了骨密度外,可能和骨骼的微结构有关。     

Association of red blood cell 5-methyltetrahydrfoate folate with bone mineral density in postmenopausal Iranian women

Recent studies have suggested that hyperhomocystenemia and low plasma folate are associated with fracture and also bone mineral density (BMD) and that they may contribute to the pathogenicity of osteoporosis in postmenopausal women. However, as plasma total homocysteine (tHcy) and plasma folate can be regarded as short-term markers when compared to a long-term variable such as BMD, in this study we tested the hypothesis that low red blood cell 5-methyltetrahydrofolate (RBC 5-MTHFR) as a long-term marker of the folate status may be a better predictor of BMD than plasma 5-MTHF, and its deficiency may contribute to the pathogenecity of osteoporosis in postmenopausal Iranian women. The BMD at the femoral neck and lumbar spine (measured by dual-energy X-ray absorptiometry, DXA) together with anthropometric and biochemical components of the homocysteine re-methylation pathway including plasma tHcy, 5-MTHF and vitamin B12, RBC 5-MTHF and creatinine were determined in 366 postmenopausal women. RBC 5-MTHF was more highly correlated with BMD at the lumbar spine ( r =0.21, P =0.001) and femoral neck ( r =0.19, P =0.004) than was plasma 5-MTHF (lumbar spine; r =0.14, P =0.03 and femoral neck; r =0.17, P =0.006). Stepwise multiple linear regression analyses revealed that RBC 5-MTHF was one of the predictors of BMD explaining 4.3 and 4.0% variance of BMD at the lumbar spine and femoral neck, respectively, whereas plasma 5-MTHF was excluded in the model and not determined to be a predictor of BMD at both the lumbar spine and femoral neck when adjusted for age, BMI, years since menopause and RBC 5-MTHF. This study suggests that RBC 5-MTHF is a better predictor of BMD than plasma 5-MTHFR when compared to a long-term marker such as BMD, and its deficiency is associated with low BMD that may contribute to the pathogenecity of osteoporosis in postmenopausal women.