Bone histomorphometry in adult patients with cystic fibrosis.

STUDY OBJECTIVE: Low bone mineral density is a common complication of cystic fibrosis (CF), and recent studies have implicated vitamin D insufficiency as a significant etiologic factor. The aim of this study was to establish whether there was bone biopsy evidence of vitamin D deficiency osteomalacia in patients with CF and to document the general histomorphometric characteristics of CF bone. PATIENTS AND METHODS: A retrospective descriptive and histomorphometric study of postmortem L2/L3 vertebral bone biopsy specimens was undertaken on tissue from 11 posttransplant CF patients and 4 nontransplanted CF patients. Control data were derived from postmortem bone specimens from 15 young adults. RESULTS: Bone from all CF patients was characterized by severe osteopenia in both trabecular and cortical bone. At the cellular level, there was decreased osteoblastic and increased osteoclastic activity. The reduction in osteoblastic activity was due to both a decrease in osteoblast number and a decrease in the biosynthetic potential of osteoblasts. The osteoclastic changes were due to an increase in the number of osteoclasts. The increase in osteoclasis and the uncoupling of osteoblastic and osteoclastic activity resulted in an increase in resorptive surfaces. Although there were few significant differences between the transplanted and nontransplanted CF groups, both cortical and trabecular bone mass tended to be lower after transplantation. None of the CF undecalcified biopsy specimens showed osteoid parameters characteristic of vitamin D deficiency osteomalacia. CONCLUSIONS: CF patients have an unusual and complex pattern of cellular changes within bone that are not typical of vitamin D deficiency osteomalacia.

Can bisphosphonate treatment be stopped in a growing child with skeletal fragility?

UNLABELLED: Cyclical pamidronate therapy in a 2-year-old child with skeletal fragility resulted in remodelling of vertebral fractures and improvement in bone mineral density (BMD) at distal radial and spinal sites. The BMD at both sites decreased precipitously within 24 months of stopping treatment, raising the question as to whether bisphosphonates can be stopped in a growing child with skeletal fragility. INTRODUCTION: At age 23 months, a male toddler sustained a low trauma fracture of his right femur. Skeletal radiographs revealed generalised osteopenia with multiple vertebral body fractures. He was diagnosed with type IV osteogenesis imperfecta; however, no mutations were found in COL1A1 or COL1A2 genes. METHODS: This case report presents bone densitometry data before, during and after bisphosphonate treatment. Axial QCT was main outcome from 2 years of age; DXA and pQCT were taken after age 5. RESULTS: QCT confirmed that he had low spinal trabecular volumetric BMD (Z-score -2.4). After 4 years of treatment his vertebral fractures had been remodelled and all bone densitometry values (QCT, DXA and pQCT) were within normal range and therefore treatment was discontinued. Shortly after this he suffered stress fractures of his left mid tibia and at the sclerotic metaphyseal line corresponding to his first APD treatment. He had marked reduction in spinal trabecular and distal radial vBMD; change in BMAD was less marked. CONCLUSION: The patient has been restarted on IV APD therapy. This case has led us to consider whether bisphosphonate therapy can be discontinued in a child with fragility fractures before his/her linear growth has ceased?

Correlation of bone histology with parathyroid hormone, vitamin D3, and radiology in end-stage renal disease.

We analyzed transiliac bone biopsy specimens from 30 end-stage renal failure patients, taken at the time of admission for CAPD training. Results were compared with values of iPTH, bone alkaline phosphatase, 1,25-dihydroxyvitamin D3, skeletal survey, quantitative computed tomography (QCT) and single photon absorptiometry (SPA) bone density measurements. Osteitis fibrosa was the most common histological diagnosis, present in 15 of the 30 patients (50%), with eight classified as "severe" and seven as "mild." Eight patients (27%) had adynamic bone lesion, four mixed renal osteodystrophy (13%), and two (7%) osteomalacia. The mean age of the adynamic group was higher than the osteitis fibrosa group (41 +/- 12.1 vs. 56 +/- 10.2 years; P < 0.01), and than the mixed group (39 +/- 7.5 vs. 56 +/- 10.2 years; P < 0.02). Levels of iPTH enabled discrimination between groups, but not between individual patients, and values correlated with bone alkaline phosphatase (r = 0.62; P < 0.001). Erosion of the terminal phalanges was seen on the plain X-rays of 7 of 15 patients with mild or severe OF, and in three patients with another diagnosis. The majority of patients (> 90%) had bone density measurements within the normal range. No significant correlation existed between QCT or SPA scores and any of the histomorphometric parameters, or iPTH. We conclude that iPTH is the most helpful non-invasive investigation in this group of patients. Plain X-ray of the hands is the most useful radiological investigation, but single measurements of bone density are not diagnostic.