Osteoporosis in ankylosing spondylitis - prevalence, risk factors and methods of assessment

Introduction

Osteoporosis can be a complication of ankylosing spondylitis (AS), but diagnosing spinal osteoporosis can be difficult since pathologic new bone formation interferes with the assessment of the bone mineral density (BMD). The aims of the current study were to investigate prevalence and risk factors for reduced BMD in a Swedish cohort of AS patients, and to examine how progressive ankylosis influences BMD with the use of dual-energy x-ray absorptiometry (DXA) of the lumbar spine in different projections.

Methods

Methods of assessment were questionnaires, back mobility tests, blood samples, lateral spine radiographs for syndesmophyte grading (mSASSS), DXA of the hip, radius and lumbar spine in anteroposterior (AP) and lateral projections with estimation of volumetric BMD (vBMD).

Results

AS patients (modified New York criteria), 87 women and 117 men, mean age 50 ± 13 years and disease duration 15 ± 11 years were included. According to World Health Organization (WHO) criteria 21% osteoporosis and 44% osteopenia was diagnosed in patients > = 50 years. Under age 50 BMD below expected range for age was found in 5%. Interestingly lateral lumbar DXA showed significantly lower BMD and revealed significantly more cases with osteoporosis as compared with AP DXA. Lumbar vBMD was not different between sexes, but women had significantly more lumbar osteoporosis measured with AP DXA (P < 0.001). Men had significantly higher mSASSS (P < 0.001). Low BMD was associated with high age, disease duration, mSASSS, Bath Ankylosing Spondylitis Metrology Index (BASMI), inflammatory parameters and low body mass index (BMI). Increasing mSASSS correlated significantly with decreasing lateral and volumetric lumbar BMD, while AP lumbar BMD showed tendency to increase.

Conclusions

Osteoporosis and osteopenia is common in AS and associated with high disease burden. Lateral and volumetric lumbar DXA are more sensitive than AP DXA in detecting osteoporosis and are less affected by syndesmophyte formation.     

Status of Bone Mineral Density in Patients Selected for Cardiac Transplantation

ObjectiveTo determine the prevalence and correlates of low bone mineral density (BMD) in ambulatory outpatients with end-stage heart failure who were awaiting cardiac transplantation.MethodsFifty-five cardiac transplant candidates with end-stage heart failure were enrolled in this study. Bone mineral density at the lumbar spine and proximal femur was determined by dual-energy x-ray absorptiometry. Laboratory studies included serum alkaline phosphatase, calcium, intact parathyroid hormone, and 25-hydroxyvitamin D.ResultsThe mean proximal femur and lumbar spine Z scores were 0.3 ± 1.1 and 0.3 ± 1.5, respectively. The mean BMD was not lower than that of the age- and sex- matched reference population. Z scores were less than -1 in 23% at the lumbar spine and 15% at the proximal femoral neck. On the basis of T scores, osteopenia (T scores between -1 and -2.5) was present in 24% (confidence interval, 13% to 35%) of patients at the lumbar spine and in 20% (confidence interval, 10% to 30%) at the proximal femur; osteoporosis (T scores of less than -2.5) was present in 4% of the study population. Half of the patients in this study sample had elevated intact parathyroid hormone levels, and a third of the patients had low 25-hydroxyvitamin D levels.ConclusionLumbar spine and hip BMD measurements were not significantly low relative to age and sex in ambulatory patients with heart failure awaiting cardiac transplantation. (Endocr Pract. 2008;14:704-712)     

Increased Bone Mineral Density in Male Patients With Idiopathic Hypogonadotropic Hypogonadism Who Undergo Sex Hormone Therapy: Findings From Cross-Sectional and Longitudinal Studies

ObjectiveThis retrospective observational study assessed the long-term impact of pulsatile gonadotropin-releasing hormone, combined gonadotropin, or testosterone replacement therapy on total hip, femoral, and lumbar bone mineral density (BMD) and Z-scores in adult men with idiopathic hypogonadotropic hypogonadism (IHH).MethodsIn the cross-sectional study, 69 patients were allocated to untreated (n = 42) and treated (n = 27) groups. The untreated group included IHH patients without hormone therapy history, while the treated group included age- and body mass index-matched patients who had received hormone therapy for at least 5 years. The longitudinal study included 53 IHH patients, and their hip and lumbar BMDs were measured several times during hormone therapy. We then evaluated the changes in their BMD.ResultsOur cross-sectional study showed that the treated group had a significantly higher BMD and Z-score for total hip, femoral neck, and lumbar spine (P < 0.001 for all) than the untreated group, and the average bone mass even reached the age-matched normal range. The prevalence of low BMD was 80.95% and 11.11% in untreated and treated groups, respectively. In the longitudinal study (N = 53), the total hip, femoral neck, and lumbar spine BMD gradually increased during treatment. The lumbar spine showed a greater increment in BMD compared with the total hip and femoral neck (P < 0.05).ConclusionSex hormone therapy improved hip and lumbar spine BMD and Z-scores in patients with IHH. The lumbar spine showed a greater improvement in BMD compared with the total hip and femoral neck.     

Bone Mineral Density in Pituitary Stalk Interruption Syndrome: The Role of Insulin-Like Growth Factor-1 and Testosterone at Different Skeletal Sites

ObjectiveThis study aimed to determine the clinical indicators influencing bone mineral density (BMD) of the lumbar spine and femoral neck in patients with pituitary stalk interruption syndrome (PSIS) who underwent multiple hormone replacement therapy (MHRT).MethodsMale patients with PSIS (n = 51) who underwent MHRT for at least 1 year were enrolled in this study. Their BMD parameters were recorded and compared with age-, weight-, and height-matched control adults. In addition, we performed multiple linear regression analysis to correlate clinical parameters with BMD parameters at 2 different sites.ResultsFifty-one patients with PSIS had a mean age of 30.39 ± 5.50 years. After 36 months of treatment, patients with PSIS who underwent MHRT had slightly lower BMD than those in the control group. Multiple linear regression models revealed a positive association between the Z-score values for the lumbar spine with treatment duration (r = 0.453, P < .001), insulin-like growth factor-1 (IGF-1) standard deviation score (SDS) values (r = 0.248, P = .038), and total testosterone level (r = 0.260, P = .036) and a positive association between the Z-score values for the femoral neck with treatment duration (r = 0.425, P < .001) and IGF-1 SDS values (r = 0.338, P = .009).ConclusionCollectively, long-term MHRT improves bone density in patients with PSIS to the normal range. A combination of recombinant human growth hormone replacement is more beneficial to the BMD than non–recombinant human growth hormone treatment. Moreover, serum IGF-1 contributes to femoral and lumbar mineralization, whereas serum testosterone plays a role in lumbar mineralization.     

Reduced trabecular bone mineral density and cortical thickness accompanied by increased outer bone circumference in metacarpal bone of rheumatoid arthritis patients: a cross-sectional study

Introduction

The objective of this study was to assess three-dimensional bone geometry and density at the epiphysis and shaft of the third meta-carpal bone of rheumatoid arthritis (RA) patients in comparison to healthy controls with the novel method of peripheral quantitative computed tomography (pQCT).

Methods

PQCT scans were performed in 50 female RA patients and 100 healthy female controls at the distal epiphyses and shafts of the third metacarpal bone, the radius and the tibia. Reproducibility was determined by coefficient of varia-tion. Bone densitometric and geometric parameters were compared between the two groups and correlated to disease characteristics.

Results

Reproducibility of different pQCT parameters was between 0.7% and 2.5%. RA patients had 12% to 19% lower trabecular bone mineral density (BMD) (P ≤ 0.001) at the distal epiphyses of radius, tibia and metacarpal bone. At the shafts of these bones RA patients had 7% to 16% thinner cortices (P ≤ 0.03). Total cross-sectional area (CSA) at the metacarpal bone shaft of pa-tients was larger (between 5% and 7%, P < 0.02), and relative cortical area was reduced by 13%. Erosiveness by Ratingen score correlated negatively with tra-becular and total BMD at the epiphyses and shaft cortical thickness of all measured bones (P < 0.04).

Conclusions

Reduced trabecular BMD and thinner cortices at peripheral bones, and a greater bone shaft diameter at the metacarpal bone suggest RA spe-cific bone alterations. The proposed pQCT protocol is reliable and allows measuring juxta-articular trabecular BMD and shaft geometry at the metacarpal bone.     

Which measuring site in ankylosing spondylitis is best to detect bone loss and what predicts the decline: results from a 5-year prospective study

Background

Studies have shown increased prevalence of osteoporosis and increased risk for vertebral fractures in patients with ankylosing spondylitis (AS). Measurements of bone mineral density (BMD) in the lumbar spine anterior-posterior (AP) projection may be difficult to interpret due to the ligamentous calcifications, and the lateral projection might be a better measuring site. Our objectives were to investigate BMD changes after 5 years at different measuring sites in patients with AS and to evaluate disease-related variables and medications as predictors for BMD changes.

Methods

In a longitudinal study, BMD in Swedish AS patients, 50?±?13 years old, was measured with dual-energy x-ray absorptiometry (DXA) at the hip, the lumbar spine AP and lateral projections, and the total radius at baseline and after 5 years. Patients were assessed with questionnaires, blood samples, and spinal radiographs for grading of AS-related alterations in the spine with the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) and assessment of vertebral fractures by the Genant score. Multiple linear regression analyses were used to investigate predictors for BMD changes.

Results

Of 204 patients included at baseline, 168 (82%) were re-examined after 5 years (92 men and 76 women). BMD decreased significantly at the femoral neck and radius and increased significantly at the lumbar spine, both for AP and lateral projections. Mean C-reactive protein during follow-up predicted a decrease in the femoral neck BMD (change in %, β?=?–0.15, p?=?0.046). Use of bisphosphonates predicted an increase in BMD at all measuring sites (p?<?0.001 to 0.013), except for the total radius. Use of tumor necrosis factor inhibitors (TNFi) predicted an increase in AP spinal BMD (β?=?3.15, p?=?0.012).

Conclusion

The current study (which has a long follow-up, many measuring sites, and is the first to longitudinally assess the lateral projection of the spine in AS patients) surprisingly showed that lateral projection spinal BMD increased. This study suggests that the best site to assess bone loss in AS patients is the femoral neck and that inflammation has an adverse effect, and the use of bisphosphonates and TNFi has a positive effect, on BMD in AS patients.

     

Efectos del tratamiento con ácido zoledrónico en pacientes adultos con osteogénesis imperfecta

Background and objectiveOsteogenesis imperfecta (OI) is a genetic disorder that results in bone fragility. Several studies have demonstrated the effectiveness of bisphosphonate therapy. The aim of this study was to evaluate the effects of intravenous zoledronic acid on bone mineral density (BMD) and biochemical markers of bone turnover in adults with OI.Material and methodsWe carried out a prospective non-randomized study in patients with osteoporosis or severe osteopenia (T score <?2) related to OI and intolerance or contraindication to oral bisphosphonates. The patients were treated with a zoledronic acid infusion every 6 months. Densitometry was carried out annually. Calcium (Ca), phosphate (P), intact parathormone (PTH), 25 hydroxyvitamin D and biochemical markers of bone turnover [bone alkaline phosphatase (BAP), beta-cross-laps (CTX) and urinary deoxypyridoxine (DOP)] were measured every year. Adverse events and new fractures were registered.ResultsTen patients (2 men and 8 women) were treated. Treatment increased BMD measured in the lumbar spine after 24 (0.738±0.141 vs 0.788±0.144 g/cm²; p=0.048) and 36 months (0.720±0.139 vs 0.820±0.128; p=0.01). Significant increases in BMD were also observed after 24 months in the femoral neck (0.677±0.121 vs 0.703±0.122 g/cm²; p<0.016). Serum Ca, P, BAP and CTX concentrations remained unchanged. PTH concentrations increased and vitamin D concentrations decreased after 36 months of treatment. DOP excretion decreased significantly after 24 months. Seven patients had mild influenza-like symptoms occurring within the first 24 h after the first infusion. No severe adverse events were observed. None of the patients had new fractures.ConclusionZoledronic acid seems to be a safe and effective treatment option in adults with osteoporosis related to OI.     

Familial comparison of bone mineral density at the proximal femur and lumbar spine

Familial resemblance of bone mineral density (BMD) was studied in the lumbar spine and three regions of the proximal femur in 41 biological mother-daughter (M-D), 42 mother-son (M-S), 24 mother-grandmother (M-G) pairs and 18 mother-grandmother-daughter (M-G-D) triads. Children were placed into three maturity categories based on an assessment of secondary sex characteristics and growth velocities. Two sets of standardized BMD Z-scores were derived for the children based on either their chronological age or their maturational status. These scores were compared with maternal Z-scores derived from age-specific norms. Similar comparisons were made between the Z-scores of the mothers and grandmothers. For all three regions of the proximal femur and for the total AP lumbar spine the correlations between Z-score values were similar and significant (P < 0.05) between the M-G and M-D pairs ranging from 0.41 to 0.57. In general, the familial correlations improved when maturity-status based Z-scores were used for comparison. The absolute BMD values measured in the grandmothers and the three maturity groups of the children — expressed as a percentage of the BMD of the mothers — showed that at the neck and the trochanteric regions of the proximal femur the late-pubescent girls and boys had a significantly (P < 0.05) greater bone density than their mothers (115–123%), whereas at the AP spine these groups averaged only 88% of their mothers BMD. This site differential was not apparent when comparing the post-menopausal grandmothers with the pre-menopausal mothers (80% at both sites). Three generation comparisons demonstrated a strong familial resemblance in bone mineral density. The value of incorporating maturity-based versus chronological-based parameters for comparison with adult measures in studies that involve growing children at different stages of development was also demonstrated.     

Correlation Between Bone Markers and Bone Mineral Density in Postmenopausal Women with Osteoporosis

ObjectiveTo study the relationship between bone markers and bone mineral density (BMD) in an effort to identify their utility in postmenopausal women with osteoporosis.MethodsEighty-two consecutive postmenopausal women with untreated osteoporosis were included in the study. Forearm, spinal, and femoral BMD by dual-energy x-ray absorptiometry and markers of bone formation (serum osteocalcin and bone-specific alkaline phosphatase) and bone resorption (urinary free deoxypyridinoline) were measured in all patients. Patients with low serum vitamin D levels, secondary osteoporosis, or clinically significant systemic disease were excluded from the study. The patients were classified on the basis of BMD of the lumbar spine into the following 3 groups: mild (n = 23) (T score -2.5 through -3), moderate (n = 42) (T score -3.1 through -4), or severe (n = 17) (T score ≤-4.1) osteoporosis. One-way analysis of variance and Pearson correlation were used for statistical analysis, with a P value < .05 being considered significant.ResultsSerum osteocalcin was significantly different among the 3 study groups (4.1 ± 2.7, 4.5 ± 3.1, and 6.7 ± 5.6 ng/mL, respectively; P = .0349) and had a significant negative correlation with BMD (r² = -0.0779; P = .0168). Other bone markers such as bone-specific alkaline phosphatase and urinary free deoxypyridinoline did not correlate with the underlying BMD.ConclusionIn our study, osteocalcin was significantly correlated with BMD in postmenopausal women with osteoporosis. Other bone markers did not correlate with BMD. Further large-scale population data and analyses are needed to confirm these findings. (Endocr Pract. 2008;14:1102-1107)     

Effects of Long-Term Alendronate Treatment on a Large Sample of Pediatric Patients with Osteogenesis Imperfecta

Objective: Osteogenesis imperfecta (OI) is a group of inherited diseases characterized by reduced bone mass, recurrent bone fractures, and progressive bone deformities. Here, we evaluate the efficacy and safety of long-term treatment with alendronate in a large sample of Chinese children and adolescents with OI.Methods: In this prospective study, a total of 91 children and adolescents with OI were included. The patients received 3 years' treatment with 70 mg alendronate weekly and 500 mg calcium daily. During the treatment, fracture incidence, bone mineral density (BMD), and serum levels of the bone turnover biomarkers (alkaline phosphatase [ALP] and cross-linked C-telopeptide of type I collagen [β-CTX]) were evaluated. Linear growth speed and parameters of safety were also measured.Results: After 3 years of treatment, the mean annual fracture incidence decreased from 1.2 ± 0.8 to 0.2 ± 0.3 (P<.01). BMD at the lumbar spine and femoral neck significantly increased by 74.6% and 39.5%, with their BMD Z-score increasing from -3.0 to 0.1 and from -4.2 to -1.3, respectively (both P<.01 vs. baseline). In addition, serum ALP and β-CTX levels decreased by 35.6% and 44.3%, respectively (both P<.05 vs. baseline). Height significantly increased, but without an obvious increase in its Z-score. Patient tolerance of alendronate was good.Conclusion: Three years' treatment with alendronate was demonstrated for the first time to significantly reduce fracture incidence, increase lumbar spine and femoral neck BMD, and decrease bone turnover biomarkers in Chinese children and adolescents with OI.Abbreviations:ALP = alkaline phosphataseβ-CTX = cross-linked C-telopeptide of type I collagenBMD = bone mineral densityBP = bisphosphonateDXA = dual-energy X-ray absorptiometry25OHD = 25-hydroxyvitamin DOI = osteogenesis imperfectaPTH = parathyroid hormone     

Bone Mineral Density of the 1/3 Radius Refines Osteoporosis Diagnosis,Correlates With Prevalent Fractures,and Enhances Fracture Risk Estimates

ObjectiveTo investigate the added value of 1/3 radius (1/3R) for the diagnosis of osteoporosis by spine and hip sites and its correlation with prevalent fractures and predicted fracture risk.MethodsFracture Risk Assessment Tool (FRAX) scores for hip and major osteoporotic fractures (MOF) with/without trabecular bone score were considered proxy for fracture risk. The contribution of 1/3R to risk prediction was depicted via linear regression models with FRAX score as the dependent variable—first only with central and then with radius T-score as an additional covariate. Significance of change in the explained variance was compared by F-test.ResultsThe study included 1453 patients, 86% women, aged 66 ± 10 years. A total of 32% (n = 471) were osteoporotic by spine/hip and 8% (n = 115) by radius only, constituting a 24.4% increase in the number of subjects defined as osteoporotic (n = 586, 40%). Prior fracture prevalence was similar among patients with osteoporosis by spine/hip (17.4%) and radius only (19.1%) (P = .77).FRAX prediction by a regression model using spine/hip T-score yielded explained variance of 51.8% and 49.9% for MOF and 39.8% and 36.4% for hip (with/without trabecular bone score adjustment, respectively). The contribution of 1/3R was statistically significant (P < .001) and slightly increased the explained variance to 52.3% and 50.4% for MOF and 40.9% and 37.4% for hip, respectively.ConclusionReclassification of BMD results according to radius measurements results in higher diagnostic output. Prior fractures were equally prevalent among patients with radius-only and classic-site osteoporosis. FRAX tool performance slightly improved by incorporating radius BMD. Whether this approach may lead to a better fracture prediction warrants further prospective evaluation.     

Does Baseline PTH Influence Recovery of Bone Mineral Density,Trabecular Bone Score and Bone Turnover Markers? A Prospective Study Following Curative PArathyroidectomy in Primary Hyperparathyroidism

Objective: This prospective study was carried out to assess trabecular bone score, bone mineral density (BMD), and bone biochemistry in Indian subjects with symptomatic primary hyperparathyroidism (PHPT), and to study the influence of baseline parathyroid hormone (PTH) on recovery of these parameters following curative surgery.Methods: This was a 2-year prospective study conducted at a tertiary care centre in southern India. Baseline assessment included demographic details, mode of presentation, bone mineral biochemistry, BMD, trabecular bone score (TBS), and bone turnover markers (BTMs). These parameters were reassessed at the end of the first and second years following curative parathyroid surgery.Results: Fifty-one subjects (32 men and 19 women) with PHPT who had undergone curative parathyroidectomy were included in this study. The mean (SD) age was 44.6 (13.7) years. The TBS, BTMs, and BMD at lumbar spine and forearm were significantly worse at baseline in subjects with higher baseline PTH (≥250 pg/mL) when compared to the group with lower baseline PTH (<250 pg/mL). At the end of 2 years, the difference between high versus low PTH groups (mean ± SD) persisted only for forearm BMD (0.638 ± 0.093 versus 0.698 ± 0.041 g/cm²; P =.01). However, on follow-up visits in the first and second year after curative parathyroidectomy, there was no significant difference in BTMs, BMD at the femoral neck, lumbar spine, and TBS between the 2 groups stratified by baseline PTH.Conclusion: The BMD at the forearm remained significantly worse in individuals with high baseline PTH even at 2 years after surgery, while other parameters including TBS improved significantly from baseline.Abbreviations: 25(OH)D = 25-hydroxyvitamin D; BMD = bone mineral density; BMI = body mass index; BTMs = Bone turnover markers; CTX = C-terminal telopeptide of type 1 collagen; DXA = dual energy X-ray absorptiometry; P1NP = N-terminal propeptide of type 1 procollagen; PHPT = primary hyperparathyroidism; PTH = parathyroid hormone; TBS = trabecular bone score     

Osteogenesis and osteoclast inhibition in rheumatoid arthritis patients treated with bisphosphonates alone or in combination with pitavastatin over an 18-month follow-up after more than 4 years of treatment with bisphosphonates

Introduction

To investigate the effects of bisphosphonates (Bis) (etidronate, alendronate, and risedronate), alone and in combination with statin, on the BMD (bone mineral density) and bone metabolism of rheumatoid arthritis (RA) patients.

Methods

Seventy-seven RA patients who had been receiving prednisolone (PSL) and Bis for over 4 years were divided into two groups: Bis and Bis + statin (n = 42 and 35; average age, 66.4 and 65.3 years; average disease duration, 24.9 and 20.8 years; average PSL dose, 2.4 and 2.7 mg, respectively). Serum levels of NTX (N-terminal telopeptide of type I collagen), TRACP-5b (tartrate-resistant acid phosphate-5b), PICP (C-terminal propeptide of type I procollagen), and RANKL (receptor activator of NF-κB ligand) were measured over an 18-month period of treatment and follow-up. The BMD levels of the two groups at the radius, lumbar spine, and femoral neck were compared using DXA (dual-energy x-ray absorptiometry).

Results

A significant increase was only observed in the BMD of the lumbar spine at 18-months, but the BMDs of the radius and femoral neck decreased during the follow-up period in the Bis group. Meanwhile, a significant increase was observed in the BMD of the lumbar spine in the Bis + statin group during administration and the BMDs of the radius and femoral neck stayed at baseline. Among the markers of bone metabolism, serum NTX was up-regulated after 6 months in the Bis + statin group. Serum TRACP-5b was significantly increased during the follow-up period in the Bis + statin group, but only at 18 months in the Bis group. Serum PICP recovered to base line in the Bis + statin group, whereas that in the Bis group did not observably recover during the post-administration follow-up, but rather decreased.

Conclusion

Our findings suggest that both bone resorption and bone formation were inhibited by long-term administration of Bis alone, whereas combination therapy with Bis + statin may be associated with a less marked inhibition of bone metabolism. Cardiovascular disease is highly prevalent in RA patients and some patients are prescribed statins and bisphosphonate. Bis + statin may confer more benefit to the bone metabolism of these patients compared to Bis alone.     

Treatment of Adult Hypophosphatasia with Teriparatide

ObjectiveTo describe the effects of 24 months of teriparatide therapy in an adult with hypophosphatasia, which thus far has no established medical treatment.MethodsA 75-year-old woman with hypophosphatasia was treated with ergocalciferol and calcium supplements for 2 years. She had sustained multiple spontaneous and low-trauma fractures since she was 10 years old. Baseline biochemical values (and reference ranges) were as follows: serum total alkaline phosphatase ranged from 14 to 17 U/L (30 to 110), bone-specific alkaline phosphatase (BSALP) was 5 U/L (14 to 43), serum phosphorus was elevated at 5.4 mg/dL (2.6 to 4.4), and pyridoxal 5′-phosphate was high at 250 ng/mL (5 to 30). At baseline, she had mild secondary hyperparathyroidism (intact parathyroid hormone, 76 pg/mL; reference range, 10 to 65), which was corrected by the calcium supplementation and vitamin D therapy. Dual-energy x-ray absorptiometry (DXA) scanning in 2003 showed L1-L4 bone mineral density (BMD) of 0.786 g/cm², T score of -3.3, and Z score of -1.7; DXA also showed femoral neck BMD of 0.740 g/cm², T score of -2.5, and Z score of -0.5. During walking, the patient sustained a low-trauma fracture in a metatarsal. Teriparatide, synthetic parathyroid hormone(1-34), in a dosage of 20 μg subcutaneously was given daily from April 2004 until June 2006.ResultsAfter about 1.5 years of teriparatide therapy, BSALP reached the lower end of the reference range at 16 U/L, and after 24 months of continuous teriparatide treatment, both serum total alkaline phosphatase and BSALP normalized at 30 U/L and 18 U/L, respectively. Pyridoxal 5′-phosphate declined from a baseline of 250 to 188 ng/mL after 17 months of treatment. Urinary N-telopeptide increased from a baseline of < 6 to 19 after 17 months and to 70 bone collagen equivalents/mmol creatinine after 24 months of anabolic therapy. Repeated DXA scanning showed a substantial improvement in lumbar spine BMD and stability in hip BMD. The patient experienced no clinical fractures or adverse events during teriparatide therapy.ConclusionIn one woman with adult hypophosphatasia, 2 years of teriparatide treatment improved bio-chemical markers of bone remodeling and increased skeletal mineralization. Teriparatide may prove to be a viable treatment for adult hypophosphatasia; thus, this intervention warrants further evaluation. (Endocr Pract. 2008;14:204-208)     

X-Linked hypophosphatemic rickets: a disease often unknown to affected patients

X-Linked hypophosphatemic rickets (XLH) is an X-linked dominant disorder that is secondary to renal phosphate wasting. Affected individuals frequently present the following characteristics: short stature, lower-extremity deformity, bone pain, dental abscesses, en-thesopathy, rickets, and osteomalacia. Since the disorder is characterized by evident phenotypic abnormalities, we hypothesized that there would be a high degree of knowledge about the disease in affected kindreds. Thus, we constructed a six-page, self-administered questionnaire to determine whether family members are, in fact, aware of their disease and properly diagnosed and treated. We also designed the survey to determine rates of symptoms thought to be associated with rickets/osteomalacia in a population with a lower referral bias than is usually seen in tertiary care centers. We administered the questionnaire to 234 study subjects (57 affected) who were members of one of three large kindreds. Although 62% of affected individuals knew they had some problem with their bones, only 22.6% were told by a physician that they had rickets or osteomalacia. This apparent lack of awareness occurred in spite of 61.1% of affected subjects complaining of bone or joint problems to their personal physician. Indeed, of those patients who had persistent complaints, only 34.5% were told they had rickets or osteomalacia. Only one patient was taking phosphate and vitamin D. The spectrum of symptoms evident in affected subjects compared with normals included: dental abscesses (54.5% vs. 13.0%, P < 0.001), bone pain (45.5% vs. 28.2%, P = 0.027), back pain (51.8% vs. 35.1%, P = 0.036), joint stiffness (48.2% vs. 16.8%, P < 0.001), joint pain (55.4% vs. 31.1%, P = 0.003), weakness (25.0% vs. 10.7%, P = 0.023), and hearing loss (28.6% vs. 9.8%, P = 0.002). Surprisingly, although affected individuals complained of many symptoms due to XLH, they fractured bones less frequently than controls (20% vs. 38.1%., P = 0.018). Our data demonstrate that, despite the presence of disease in family members, few affected subjects knew that they had XLH. Although the presence of symptoms did increase knowledge of disease status, only one-third of symptomatic individuals knew of their diagnosis.     

Effect of cervus and cucumis polypeptide combined with zoledronic acid on bone metabolic biochemical markers in glucocorticoids – Induced osteoporosis patients

ObjectiveTo investigate the effect of cervus and cucumis polypeptide combined with zoledronic acid on bone metabolic biochemical markers in glucocorticoids - induced osteoporosis patients.MethodsA total of 100 patients with glucocorticoids - induced osteoporosis admitted to our hospital from January 2015 to June 2017 were enrolled in this study. Patients were divided into observation group and control group by random number table method, 50 cases in each group. Patients in the observation group were treated with deer melon polypeptide in combination with zoledronic acid, and patients in the control group were treated with zoledronic acid alone. The patients in both groups were treated for 2 months. The changes of bone mineral density (BMD) and biochemical markers of bone metabolism in lumbar vertebrae L1-4, left femoral neck and large trochanter were analyzed before and after treatment.ResultsThe pre- BMD at lumbar spine L_1-4, left femoral neck and great trochanter had no statistic difference (P > 0.05), the BMD at each sites improved after treatment, and the difference were statistical before and after treatment (P < 0.05). BMD at above sites of two groups after treatment had statistical difference (P < 0.05), and the BMD at lumbar spine L_1-4, left femoral neck and great trochanter in the observation group was higher than that of the control group. There were no significant differences in PTH, 25-(OH)D3, TRACP, β-CTX and BGP levels between the two groups before treatment (P > 0.05). The levels of 25-(OH)D3, TRACP, β-CTX and BGP in the two groups were significantly improved after treatment (P < 0.05), and the levels of PTH, TRACP and β-CTX in the observation group were significantly lower than those in the control group. The levels of 25-(OH) D3 and BGP were significantly higher than those of the control group (P < 0.05).ConclusionThe cervus and cucumis polypeptide combined with zoledronic acid can improve the BMD at lumbar spine L_1-4, left femoral neck and great trochanter, and ameliorate the bone metabolic biochemical markers for patients with glucocorticoids - induced osteoporosis.     

2型糖尿病骨密度与冠状动脉钙化积分相关性研究

目的:探讨2型糖尿病患者冠脉钙化积分与骨密度的关系。方法:入选在2015年6月至2017年6月我科住院的2型糖尿病患者98例,按照性别以及糖化血红蛋白8%、低密度脂蛋白2.6 mmol/L、身高体重指数24 kg/m2为切点分为两组,进行冠脉动脉CT检查,计算冠脉动脉总钙化积分,依照钙化积分等于0为阴性组,大于0为阳性组。同时检测患者的骨密度、骨代谢指标、血钙、血磷等水平。比较冠脉钙化积分和骨代谢指标及骨密度的相关性。结果:1)男性患者中:阳性组糖化血红蛋白和颈部血管斑块形成明显高于阴性组,差异有统计学意义。女性患者中:阳性组年龄、颈部血管内膜厚度、高血压病史明显高于阴性组,差异有统计学意义。2)阳性、阴性两组之间骨代谢指标差异无统计学意义。3)男性患者中:阳性组腰椎骨密度明显高于阴性组,差异有统计学意义。女性患者中阳性组的腰椎骨密度明显低于阴性组,差异有统计学意义,在控制混杂因素以后,两组间差异无统计学意义。4)分别在男性和女性患者中按照年龄为60岁分为两组,两组间阳性组与阴性组的骨代谢指标及骨密度差异无统计学意义。结论:在2型糖尿病患者中,冠脉钙化积分和骨代谢以及骨密度之间无明显相关性。     

Long-Term Follow-up of patients on Drug Holiday from Bisphosphonates: Real-World Setting

ObjectiveAtypical femoral fractures and osteoporosis of the jaw have been associated with prolonged bisphosphonate therapy for postmenopausal osteoporosis. American Association of Clinical Endocrinologists guidelines suggest a drug holiday after 4 to 5 years of bisphosphonate treatment for moderate-risk patients and 10 years for high-risk patients, but there are minimal data on safe holiday durations. A recent U.S. Food and Drug Administration perspective suggests a treatment duration of 3 to 5 years. Our aim was to describe a group of patients on drug holiday and identify fracture risk.MethodsA retrospective chart review was conducted of 209 patients who started a bisphosphonate drug holiday between 2005 and 2010. Collected data included bone mineral density (BMD), markers of bone turnover, vitamin D status, and clinical and radiographic reports of fractures.ResultsEleven of 209 patients (5.2%) developed a fracture. Their mean age was 69.36 years (±15.58), and the mean lumbar spine and femoral neck T-scores were −2.225 (±1.779) and −2.137 (±0.950), respectively. All patients had a significant increase in bone-specific alkaline phosphatase at 6 months, which was more pronounced in the fracture group (3.0 ± 0.6083 μg/L vs. 1.16 ± 1.9267 μg/L). Over 4 years, there was no significant change in mean lumbar spine BMD for the entire cohort, but there was a statistically significant decline in the femoral neck BMD at year 2 (−0.0084 ± 0.03 gm/cm²).ConclusionThe current practice of initiating BP holidays needs further evaluation, particularly in the real-world setting. Elderly patients and those with very low BMD warrant close follow-up during a drug holiday. A fracture, early significant rise in bone turnover markers, and/or a decline in BMD should warrant resumption of osteoporosis therapy. (Endocr Pract. 2013;19:989-994)     

The usefulness of bone metabolic indices for the prediction of changes in bone mineral density after parathyroidectomy in patients with primary hyperparathyroidism.

Patients with primary hyperparathyroidism (pHPT) have reduced bone mineral density (BMD). Although pHPT causes high bone turnover, the exact metabolic bone markers useful for predicting changes in BMD after parathyroidectomy (PTX) remain elusive. The present study was performed to examine the relationship between bone metabolic indices and BMD changes after PTX in 29 pHPT Japanese patients, which received PTX successfully. BMD values were measured by dual-energy X-ray absorptiometry in the lumbar spine and distal one third of radius. As for bone metabolic indices, serum bone-type alkaline phosphates (BAP), serum osteocalcin (OCN), urinary deoxypiridinoline (Dpd), and urinary type I collagen cross-linked N-telopeptides (NTX) were measured. The study included 10 male and 19 female patients (17 postmenopausal). Urinary Dpd, but not NTX was significantly correlated with serum BAP and OCN. Either bone formation or bone resorption indices were significantly and highly correlated with Z-score of BMD in the radius, but not at lumbar spine. Urinary Dpd was significantly correlated with BMD changes at both lumbar spine and radius and at all time points over the two years after PTX. These correlations were most potent among bone metabolic indices in this study. The measurement of urinary Dpd would be useful for predicting long-term changes in BMD at radial and lumbar spine after PTX than other bone metabolic indices.     

Zoledronic Acid Versus Alendronate In The Treatment of Children With Osteogenesis Imperfecta: A 2-Year Clinical Study

Objective: Bisphosphonates have been demonstrated to increase the bone mineral density (BMD) of osteogenesis imperfecta (OI) patients. We aimed to compare the efficacy and safety of intravenous zoledronic acid and oral alendronate in patients with OI.Methods: A total of 161 patients with OI ranging from 2 to 16 years old were included and randomized at a 2:1 ratio to receive either weekly oral alendronate (ALN) 70 mg or a once-yearly infusion of zoledronic acid (ZOL) for 2 years. The primary endpoints were percentage change from baseline in lumbar spine (LS) BMD and change in Z-scores of LS BMD.Results: A total of 136 patients with OI completed the 2-year clinical study, 90 of whom were assigned to receive ALN, while 46 received ZOL treatment. The percentage change in LS BMD was 60.01 ± 7.08% in the ALN group and 62.04 ± 5.9% in the ZOL group (P = .721). The corresponding BMD Z-score increased by 0.50 ± 0.05 in the ALN group and 0.71 ± 0.06 in the ZOL group (P = .013). ZOL was superior to ALN in reducing the clinical fracture rate (hazard ratio, 0.23; 95% confidence interval, 0.118 to 0.431). There was no difference in the incidence of severe side effects between the two groups.Conclusion: A once-yearly 5 mg infusion of ZOL and weekly oral ALN had similar effects in increasing BMD and reducing bone resorption in children and adolescents with OI. ZOL was superior to ALN in reducing the clinical fracture rate.Abbreviations: 25OHD = 25-hydroxyvitamin D; ALN = alendronate; ALP = alkaline phosphatase; β-CTX = cross-linked C-telopeptide of type I collagen; BMD = bone mineral density; BP = bisphosphonate; FN = femoral neck; LS = lumbar spine; OI = osteogenesis imperfecta; SAE = severe adverse event; ZOL = zoledronic acid