Parathyroidectomy improves bone geometry and microarchitecture in female patients with primary hyperparathyroidism: a one-year prospective controlled study using high-resolution peripheral quantitative computed tomography

Following parathyroidectomy (PTX), bone mineral density (BMD) increases in patients with primary hyperparathyroidism (PHPT), yet information is scarce concerning changes in bone structure and strength following normalization of parathyroid hormone levels postsurgery. In this 1‐year prospective controlled study, high‐resolution peripheral quantitative computed tomography (HR‐pQCT) was used to evaluate changes in bone geometry, volumetric BMD (vBMD), microarchitecture, and estimated strength in female patients with PHPT before and 1 year after PTX, compared to healthy controls. Twenty‐seven women successfully treated with PTX (median age 62 years; range, 44–75 years) and 31 controls (median age 63 years; range, 40–76 years) recruited by random sampling from the general population were studied using HR‐pQCT of the distal radius and tibia as well as with dual‐energy X‐ray absorptiometry (DXA) of the forearm, spine, and hip. The two groups were comparable with respect to age, height, weight, and menopausal status. In both radius and tibia, cortical (Ct.) vBMD and Ct. thickness increased or were maintained in patients and decreased in controls (p < 0.01). Radius cancellous bone architecture was improved in patients through increased trabecular number and decreased trabecular spacing compared with changes in controls (p < 0.05). No significant cancellous bone changes were observed in tibia. Estimated bone failure load by finite element modeling increased in patients in radius but declined in controls (p < 0.001). Similar, albeit borderline significant changes in estimated failure load were found in tibia (p = 0.06). This study showed that females with PHPT had improvements in cortical bone geometry and increases in cortical and trabecular vBMD in both radius and tibia along with improvements in cancellous bone architecture and estimated strength in radius 1 year after PTX, reversing or attenuating age‐related changes observed in controls. © 2012 American Society for Bone and Mineral Research.     

Bone geometry, density, and microarchitecture in the distal radius and tibia in adults with osteogenesis imperfecta type I assessed by high-resolution pQCT

Osteogenesis imperfecta (OI) is a hereditary disorder characterized by decreased biosynthesis or impaired morphology of type I collagen that leads to decreased bone mass and increased bone fragility. We hypothesized that patients with OI have altered bone microstructure and bone geometry. In this cross‐sectional study we compared patients with type I OI to age‐ and gender‐matched healthy controls. A total of 39 (13 men and 26 women) patients with OI, aged 53 (range, 21–77) years, and 39 controls, aged 53 (range, 21–77) years, were included in the study. Twenty‐seven of the patients had been treated with bisphosphonates. High‐resolution peripheral quantitative computed tomography (HR‐pQCT) at the distal radius and distal tibia and dual‐energy X‐ray absorptiometry of total hip, femoral neck, trochanteric region, and the lumbar spine (L1–L4) were performed. The patients were shorter than the controls (159 ± 10 cm versus 170 ± 9 cm, p < 0.001), but had similar body weight. In OI, areal bone mineral density (aBMD) was 8% lower at the hip (p < 0.05) and 13% lower at the spine (p < 0.001) compared with controls. The trabecular volumetric bone mineral density (vBMD) was 28% lower in radius (p < 0.001) and 38% lower in tibia (p < 0.001) in OI compared with controls. At radius, total bone area was 5% lower in OI than in controls (p < 0.05). In the tibia, cortical bone area was 18% lower in OI (p < 0.001). In both radius and tibia the number of trabeculae was lower in patients compared to the controls (35% and 38%, respectively, p < 0.001 at both sites). Furthermore, trabecular spacing was 55% higher in OI in both tibia and radius (p < 0.001 at both sites) when compared with controls. We conclude that patients with type I OI have lower aBMD, vBMD, bone area, and trabecular number when compared with healthy age‐ and gender‐matched controls. © 2012 American Society for Bone and Mineral Research.     

Strontium ranelate reduces the risk of vertebral and nonvertebral fractures in women eighty years of age and older.

Strontium ranelate produces an early and sustained reduction of both vertebral and nonvertebral fractures in patients > or = 80 years of age. INTRODUCTION: About 25-30% of the population burden of all fragility fractures in the community arise from women > or = 80 years of age, because this population is at high risk for all types of fracture, particularly nonvertebral fractures. Despite this, evidence that therapies reduce the risk of both vertebral and nonvertebral fractures in this group is lacking. The aim of this study was to determine whether strontium ranelate, an agent that reduces the risk of vertebral and nonvertebral fractures in postmenopausal women >50 years of age, also reduces fractures in the elderly. MATERIALS AND METHODS: An analysis based on preplanned pooling of data from two international, phase III, randomized, placebo-controlled, double-blind studies (the Spinal Osteoporosis Therapeutic Intervention [SOTI] and TReatment Of Peripheral OSteoporosis [TROPOS]) included 1488 women between 80 and 100 years of age followed for 3 years. Yearly spinal X-rays were performed in 895 patients. Only radiographically confirmed nonvertebral fractures were included. RESULTS: Baseline characteristics did not differ in placebo and treatment arms. In the intent-to-treat analysis, the risk of vertebral, nonvertebral, and clinical (symptomatic vertebral and nonvertebral) fractures was reduced within 1 year by 59% (p = 0.002), 41% (p = 0.027), and 37% (p = 0.012), respectively. At the end of 3 years, vertebral, nonvertebral, and clinical fracture risks were reduced by 32% (p = 0.013), 31% (p = 0.011), and 22% (p = 0.040), respectively. The medication was well tolerated, and the safety profile was similar to that in younger patients. CONCLUSIONS: Treatment with strontium ranelate safely reduces the risk of vertebral and nonvertebral fractures in women with osteoporosis > or = 80 years of age. Even in the oldest old, it is not too late to reduce fracture risk.     

Ultrastructural investigations of bone resorptive cells in two types of autosomal dominant osteopetrosis

In order to investigate the ultrastructure of bone resorptive cells in the two types of adult benign human osteopetrosis, iliac crest biopsies were obtained from 11 patients and 10 normal males, who served as a control group. Six patients had the radiological type I (4 women, 2 men, aged 23–58 years, MEAN = 36.5 years), and 5 type II disease (5 men, aged 20–48 years, MEAN = 29.8 years). The normal controls (aged 23–48 years, mean 34.1 years) were recruited from the medical staff. The biopsies were immediately divided. From each patient, half was embedded in paraffin for histochemistry and light microscopy, and half in epon for transmission electron microscopy.

The osteoclasts were markedly reduced in number and size hi Type I disease (0.2 ± .7 cells vs. 2.9 ± 1.0 cells per 2.7 mm² of bone area, p < 0.01) compared to controls, and stained only weakly for tartrate-resistant acid phosphatase (TRAP). At the ultrastructural level, no signs of active bone resorption were identified, whereas numerous mononuclear cells were observed at the bone surfaces.

In type II disease, the osteoclasts were large and highly multi-nucleated, with an increased number (8.3 ± 2.3 cells vs. 2.9 ± 1.0. cells per 2.7 mm² of bone area, p < 0.01) compared to controls. In all patients with this type, but never in type I or in the controls, a smooth, TRAP-positive substance was seen between the osteoclasts and the bone surface. Ultrastructurally, this substance was amorphous, with a condensation along the cell membrane. Neither ruffled borders nor clear zones were identified. Nuclear inclusions resembling tubular structures were observed in some osteoclasts in all patients with type II disease.

It is concluded that characteristic differences exist between the two types of adult human osteopetrosis at the ultrastructural level. Type I is morphologically similar to some murine mutations characterized by defective maturation of bone resorptive cells. In type II, a defect in the resorptive capacity of their giant osteoclasts is proposed. The pathogenetical significance of nuclear inclusions in type II osteoclasts is unknown.     

MTHFR c.677C>T polymorphism as an independent predictor of peak bone mass in Danish men--results from the Odense Androgen Study

The MTHFR c.677C>T polymorphism has been shown to have significant effects on skeletal health in middle-aged to elderly women and men. Despite an accumulating amount of data on MTHFR genetics and the association between homocysteine levels and fracture, it remains unknown if MTHFR c.677C>T genotype affects bone mineral accretion in youth or bone loss in adulthood. The purpose of this cross-sectional study was to examine the effects of this common allelic polymorphism on peak bone mass and bone turnover. We performed MTHFR genotyping in 780 healthy Danish men, aged 20 to 29 years, participating in the Odense Androgen Study. BMD at the spine, hip and whole-body was measured using a Hologic QDR-4500 densitometer. Genotype frequencies were compatible with Hardy-Weinberg equilibrium. Spine BMD was significantly associated with genotype, with a decrease in BMD of 0.20 SD for each copy of the T-allele. Effects were independent of age, BMI, smoking and serum levels of vitamin D and IGF-I. Associations with BMD of the hip and whole body were short of statistical significance. MTHFR genotype showed no association with the bone turnover markers 1-CTP, bone specific alkaline phosphatase or osteocalcin. In conclusion, significant skeletal effects of this common polymorphism were present at the lumbar spine in men at the age of 25 years.     

Cost-effectiveness of alendronate in the prevention of osteoporotic fractures in Danish women

Pharmacological interventions for osteoporosis may reduce morbidity and mortality, but they incur additional health care costs. The aim was to quantify the additional costs and health benefits of prescribing alendronate 10 mg and calcium/vitamin D daily for 71-year-old women with a fracture risk twice that of the population average in stead of calcium/vitamin D alone. A state transition model based primarily on Scandinavian data was developed. Women were followed from age of 71 years until 100. Alendronate was assumed to reduce the fracture risk by 50%. Health benefits from the interventions were expressed in terms of life years, quality adjusted life years, and fractures avoided. Societal costs were estimated using literature estimates and Danish tariffs. All costs were measured in 2002 Danish Kroner (DKK). Future costs and benefits were discounted at 5% per year. The incremental cost per QALY gained was DKK125,000 while the cost per life year gained was DKK 374,000. The use of alendronate was cost-saving when 1) the treatment was extended to five years, 2) the risk of fracture was four times the population average, 3) the effect of alendronate was assumed to persist for three years after discontinuation of treatment, 4) a greater proportion had severe sequelae after a hip fracture, or 5) the start of therapy was delayed until age of 77 years. In conclusion, the use of alendronate compares well with other well established therapies in terms of cost-effectiveness in older women with high risk of fracture.     

The Combination of Structural Parameters and Areal Bone Mineral Density Improves Relation to Proximal Femur Strength: An In Vitro Study with High-Resolution Peripheral Quantitative Computed Tomography

The aim of this study was to assess structural indices from high-resolution peripheral quantitative computed tomography (HR-pQCT) images of the human proximal femur along with areal bone mineral density (aBMD) and compare the relationship of these parameters to bone strength in vitro. Thirty-one human proximal femur specimens (8 men and 23 women, median age 74 years, range 50–89) were examined with HR-pQCT at four regions of interest (femoral head, neck, major and minor trochanter) with 82 μm and in a subgroup (n = 17) with 41 μm resolution. Separate analyses of cortical and trabecular geometry, volumetric BMD (vBMD), and microarchitectural parameters were obtained. In addition, aBMD by dual-energy X-ray absorptiometry (DXA) was performed at conventional hip regions and maximal compressive strength (MCS) was determined in a side-impact biomechanical test. Twelve cervical and 19 trochanteric fractures were confirmed. Geometry, vBMD, microarchitecture, and aBMD correlated significantly with MCS, with Spearman’s correlation coefficients up to 0.77, 0.89, 0.90, and 0.85 (P < 0.001), respectively. No differences in these correlations were found using 41 μm compared to 82 μm resolution. In multiple regression analysis of MCS, a combined model (age- and sex-adjusted) with aBMD and structural parameters significantly increased R ² values (up to 0.90) compared to a model holding aBMD alone (R ² up to 0.78) (P < 0.05). Structural parameters and aBMD are equally related to MCS, and both cortical and trabecular structural parameters obtained from HR-pQCT images hold information on bone strength complementary to that of aBMD.     

Prevalence of risk factors for fractures and use of DXA scanning in Danish women. A regional population-based study

Summary  

To determine the relationship between risk factors and use of DXA scans. Our study showed a relatively high use of DXA in low-risk women and the relatively low coverage in women with multiple risk factors. Moreover, distance to DXA clinics, age, and socio-economic factors are associated with the use of DXA.