Iliac Crest Bone Biopsies Research Articles

Clinical and radiologic characteristics of bone metastases in breast cancer.

Metastatic bone disease was evaluated in 380 consecutive patients at the time of first metastasis of breast cancer. Studies included radiographic examination, radionuclide examination, and bone marrow biopsy. Radiographs of the skeleton demonstrated metastases in 120 patients (32%), and in 40 of these patients (13%) the bone was the only site of metastases. The diagnostic efficiency was 82% for bone scanning, 80% for pain evaluation, 59% for s-calcium analyses, and 77% for s-alkaline phosphatase analyses. Bone scanning is an effective method to exclude metastatic bone disease (sensitivity: 96%). A positive scan, however, requires radiologic confirmation (specificity: 66%). Bone scanning of the skeleton should be the initial staging procedure in all patients with recurrent breast cancer with no clinical or biochemical signs of bone metastases. Bilateral posterior iliac crest bone marrow aspirations and bone biopsies were positive in 82 out of the 320 patients who underwent biopsy. The frequency of positive bone marrow biopsy was significantly correlated with both the site of radiographic metastases and with the total number of involved bone regions. Routine bone marrow biopsies are indicated in patients with a positive bone scan, but a negative x-ray examination. In these cases biopsies should be performed bilaterally.

Heterogeneity of bone histology in parenteral nutrition patients

The characteristics of bone disease associated with parenteral nutrition are controversial. To further elucidate the contribution of aluminum deposition to this syndrome and the spectrum of pathology in patients supported by current regimens utilizing crystalline amino acids, quantitative histomorphometry and staining for Al were performed on iliac crest bone biopsies from 26 long-term parenteral nutrition patients and 16 normal volunteers. Compared with normal subjects, median trabecular bone area (TBA) for a group with positive Al staining (n = 14) who were exposed to casein hydrolysate was significantly less (12.9% vs 20.7, p less than 0.05) as was the median rate of bone formation (RBF) (29 micron2 X mm-2 X d-1 vs 360, p less than 0.05). A variety of abnormal histological findings were present in patients without positive aluminum stains (n = 12) who were supported solely by regimens utilizing crystalline amino acids. However, neither decreased TBA (median TBA = 15.3%) nor decreased RBF (median RBF = 126 micron2 X mm-2 X d-1) was uniformly characteristic of the latter patient group.

Spontaneous release of interleukin 1 from human blood monocytes reflects bone formation in idiopathic osteoporosis.

Osteoporosis is a state of reduced skeletal mass characterized by various rates of bone remodeling. Multiple locally elaborated factors have been identified that appear to influence the cellular events in bone remodeling. The possible role(s) of these factors in the pathogenesis of osteoporosis is unknown. One such factor, interleukin 1 (IL-1), is of particular interest, as this protein is known to stimulate bone resorption and perhaps formation. Consequently, we have measured the spontaneous secretion of IL-1 activity by cultured peripheral blood monocytes obtained from 22 osteoporotic patients and 14 age-matched control subjects. Monocytes from osteoporotic patients produced more IL-1 than did monocytes from control subjects. When patients were grouped according to monocyte-produced IL-1 activity, dynamic parameters of bone formation, as judged by quantitative histomorphometric analysis of iliac crest bone biopsies and by circulating levels of bone 4-carboxyglutamic acid protein (BGP)--a marker of bone formation--were higher in subjects with elevated IL-1 activity; whereas, indices of bone resorption and static indices of bone formation were similar in subjects with either high or normal IL-1 activity. IL-1 activity released by peripheral blood monocytes appears to reflect bone formation rate in osteoporotic patients and may be of pathogenetic significance in a subset of individuals with osteoporosis.

Osteomalacia and femoral neck fractures in the elderly patient.

In a series of over 1000 elderly patients with femoral neck fracture, who were routinely screened by iliac crest bone biopsy, a 2% prevalence of osteomalacia was found. This low figure suggests that osteomalacia is not a significant predisposing factor in the development of these fractures and that routine screening is not cost-effective.

Osteoblastic insufficiency is responsible for maintenance of osteopenia after loss of ovarian function in experimental beagle dogs.

Bone loss developing after cessation of ovarian function in humans represents a major health problem. To establish the value of ovariohysterectomy in female beagle dogs as a model for bone loss and to study static and dynamic parameters of bone associated with the negative bone balance occurring after cessation of ovarian function, we performed iliac crest bone biopsies before and 4 months after ovariohysterectomy in eight beagle dogs and in five sham-operated controls. Cessation of ovarian function was documented by an increase in serum levels of LH 4 weeks after ovariohysterectomy. There was no change in serum calcium, phosphorus, and creatinine during the 4 months of the study. Cancellous bone mass and trabecular mean wall thickness decreased significantly after ovariohysterectomy (P less than 0.01). In addition, the number of osteoblasts was increased and the bone formation rate per osteoblast, that is, the activity of bone-forming cells, was decreased (P less than 0.01). Parameters of bone resorption were not significantly altered in the animals with ovariohysterectomy. No changes in histomorphometric parameters of bone structure, formation or resorption were observed in the sham-operated controls. These data indicate that ovariohysterectomy in beagle dogs may serve as a useful model for bone loss associated with cessation of ovarian function. Osteoblastic insufficiency appears to play a major role in the maintenance of bone loss occurring after ovariohysterectomy in beagle dogs.

A simple method for correlative light and scanning electron microscopy of human iliac crest bone biopsies: Qualitative observations in normal and osteoporotic subjects

Despite the fact that the scanning electron microscope (SEM) offers a number of unique advantages for the investigation of bone structure, this instrument has seldom been applied in studies of the iliac crest bone biopsy. Here we describe a very simple method of preparing iliac crest biopsies for examination in the SEM after the routine histomorphometric analysis has been performed. With observations on biopsies from normal subjects and patients with osteoporosis, the paper illustrates the potential of the method for performing correlative light and scanning electron microscopical studies and for gaining new information on the three-dimensional architecture of trabecular bone.

Hypophosphatemic osteomalacia complicating von Recklinghausen's neurofibromatosis: Increase in spinal density on treatment

A 62-year-old white male with neurofibromatosis presented with multiple fractures and bone pain. He was found to have hypophosphatemic osteomalacia secondary to a renal tubular phosphate leak and was treated with phosphate, 1,25-dihydroxycholecalciferol and calcium. With treatment, his dual photon vertebral bone density increased markedly over 12 months. Repeat iliac crest bone biopsies showed that improvement in bone histology was predominantly cortical. This suggests that dual photon absorptiometry of the spine may be markedly influenced by changes in cortical bone status.

Normal vertebral body size and compressive strength: Relations to age and to vertebral and iliac trabecular bone compressive strength

Three thoracic (T 5−T 7) and three lumbar (L 1−L 3) vertebral bodies and the anterior parts of both iliac crests were removed from 44 normal individuals aged 15–87 years who had died suddenly. Small, cylindrical samples of trabecular bone (length 5 mm, diameter 7 mm) from T 6, L 1, and L 3 and from the standard site for iliac crest biopsies were compressed in an Alwetron-250 materials testing machine. Whole vertebral bodies from T 5, T 7, and L 2 with cut planoparallel end-plates were compressed in an Instron materials testing machine. The maximum compressive stress value σ max of the whole vertebral bodies and of the vertical vertebral trabecular bone decreased with age with almost parallel linear regression lines. At any age the σ max for whole vertebral bodies was about 1.6 MPa (1 MPa = 100 N cm 2 ) higher than for the trabecular bone. The average cross-sectional area of the vertebral bodies increased by 25–30% from the age of 20 to 80 years. The anisotropic properties of the vertebral trabecular bone (expressed as the ratio between the vertical and horizontal σ max) increased markedly with age. A highly significant positive correlation was observed between the vertical vertebral trabecular bone σ max (x) and the total vertebral body σ max (y = 0.90x + 1.75, r = 0.88, P < 0.01). The slope was not significantly different from 1, whereas the intercept was positive ( P < 0.01). The average total vertebral body σ max (range 1.5–7.8 MPa) could be predicted from mechanical tests on horizontal iliac crest bone biopsies with standard error of estimate (SEE) of 0.92 MPa. The study shows that the compressive strength of whole vertebral bodies depends mainly on the trabecular bone compressive strength, which decreases with age. The increase in vertebral trabecular bone anisotropy with age and the continuous periosteal growth will to some extent compensate for the obligatory age-related loss of vertebral trabecular bone mass. In normal individuals the average vertebral body compressive strength can be estimated from mechanical tests on horizontal iliac crest bone biopsies in spite of these age-related changes in internal and external architecture.

Mechanisms underlying the effects of phosphate and calcitonin on bone histology in postmenopausal osteoporosis

The aim of this study was to evaluate the mechanism underlying the beneficial effect of phosphate combined with calcitonin on trabecular bone mass in postmenopausal osteoporosis. Histomorphometric parameters of trabecular bone formation and resorption were assessed blindly on sections from tetracycline-labeled iliac crest bone biopsies from 44 women with postmenopausal osteoporosis obtained before and after 6 months of treatment with phosphate ( n = 9), calcitonin ( n = 13), combined therapy ( n = 13), or double placebos ( n = 9). Treatment with phosphate (1.5 g/day) increased the osteoblastic surface in correlation with the fractional trabecular surface with double tetracycline labeling. The mean wall thickness of the basic structural units increased significantly only in the two groups of patients treated with phosphate. Thus, oral phosphate therapy stimulated bone formation by increasing both the bone-forming surfaces and bone matrix production. The mean interstitial bone thickness, which is inversely related to the depth of resorbing cavities, was increased in the two groups treated with calcitonin (50 IU × 5 days every third week), indicating that calcitonin therapy partially inhibited the resorbing activity of osteoclasts. The combination of calcitonin and phosphate produced a reduction in bone resorption associated with a stimulation of bone matrix production. This effect resulted in a 22.1% increase in the thickness of the trabeculae and a 31.1% increase in trabecular bone volume. The data show that calcitonin combined with phosphate increased the trabecular bone volume in postmenopausal osteoporosis through reduction of bone resorption associated with stimulation of bone formation along the trabecular bone surface.

Vitamin D metabolism and osteomalacia in cystic fibrosis

A 25-yr-old black man with cystic fibrosis and cirrhosis developed symptoms of osteomalacia and hypocalcemia, hypophosphatemia, secondary hyperparathyroidism, and low circulating 25-hydroxyvitamin D (25-OHD). Serum 1,25-dihydroxyvitamin D (1,25-[OH]2D) was within the normal range. Iliac crest bone biopsy confirmed the diagnosis of osteomalacia. Oral administration of 50,000 IU of vitamin D2 failed to relieve symptoms or raise serum 25-OHD levels to normal. Intramuscular vitamin D2, 10,000 IU every 8–12 week, improved symptoms, raised serum 25-OHD to normal, and increased circulating 1,25-[OH]2D to values five times normal. Over the next 10 mo circulating 1,25-[OH]2D remained elevated despite normalization of serum calcium, phosphorus, and parathyroid hormone. Repeat bone biopsy 1 yr after parenteral vitamin D showed healing of the osteomalacia. Malabsorption of vitamin D appears secondary to profound steatorrhea due to pancreatic insufficiency and secondary biliary cirrhosis. Although extensive hepatocellular disease was present, hepatic conversion of vitamin D to 25-OHD was intact. Both high and low circulating 1,25-[OH]2D levels during active osteomalacia have been reported; initially, the level was in the normal range and higher values in this patient occurred with repletion of 25-OHD substrate. This study shows that symptomatic osteomalacia may be a major manifestation of cystic fibrosis in those patients surviving into adulthood. Measurements of serum 25-OHD in cystic fibrosis patients may identify those who should receive supplemental vitamin D.

Osteoclast enlargement in endstage renal disease

In normal subjects and patients with endstage renal disease, osteoclast cell volumes were constructed using serial 2-micron thick plastic embedded sections from iliac crest bone biopsy specimens. Four cells randomly selected from each of the subjects were analyzed to give both the cell volume from the cumulative areas and thickness of each cell slice and also the cell axes taking the vector along the bone face as width or Y, thickness from the bone surface as breadth or X and vertical dimension length or Z. The mean cell volume was 6,230 microns3 in the control subjects and was significantly larger being 11,730 microns3 and 13,680 microns3 in the two patient groups. The cells showed polarity with the largest axes, Y and Z, being those in apposition to the bone surface. Howship's lacunae were enlarged in the patients and the cross-sectional area of an individual lacuna corresponded to the area of the contiguous osteoclast, r = 0.62, P less than 0.001. All patients had secondary hyperparathyroidism and osteoclast numbers were increased. There was no correlation between osteoclast size and duration of renal failure, previous vitamin D intake, or aluminum exposure. It is suggested that in ESRD, osteoclasts undergo both an increase in number and size and that these cells, being larger, remove more bone than the smaller cells in normal subjects.

Trabecular bone remodeling and bone balance in hyperthyroidism

In vivo tetracycline double-labeled iliac crest bone biopsies from 15 hyperthyroid patients were used for the reconstruction of curves describing the variation of resorption depth and formation thickness with time. The curves emerging were compared to curves reconstructed from 13 age- and sex-matched normal individuals (mean age 44 years). The median function period for resorptive cells in hyperthyroid patients (16 days) was about one-third the resorptive period in normals (51 days). No significant difference between the osteoclast-, mononuclear-, or preosteoblast-like cell resorption depths could be demonstrated between the two groups. Consequently, the median resorption rate in hyperthyroid patients (3.8 μm/day) was more than 3 times higher than the value in the control group (1.1 μm/day). Median Sigma f, was shorter in the hyperthyroid group (109 days) than in the control group (151 days, P < 0.05), as was the median initial mineralization lag time (5 and 16 days, respectively, P < 0.01). No significant difference between the measured mean completed wall thickness (mcwT) values in the hyperthyroid groups and the control group could be demonstrated (58.1 and 60.5 μm respectively). Median initial mineralization rate in the hyperthyroid group (1.2 μm 3/μm 2 per day) was not significantly higher than the value calculated in the control group (0.9 μm 3/ μm 2 per day), but median initial matrix appositional rate in hyperthyroids (4.8 μm 3/μm 2 per day) was 3 times higher than the value calculated for normals (1.6 μm 3/μm 2 per day) ( P < 0.01). Direct measurements of mean completed wall thickness in the hyperthyroid group gave results (58.1 μm) that were not in accordance with the mean completed wall thickness calculated from the growth curve (52.1 μm, P < 0.02). In normals no such discrepancy could be demonstrated. Using the mcwT value estimated from the growth curve, the bone formation period was calculated to 90 days for hyperthyroid patients. This maximal estimate for mcwT was also significantly lower than the mean resorption depth measured in the hyperthyroid group (61.7 μm, P < 0.05), which means that a net negative balance per remodeling cycle existed in the hyperthyroid group. Bone balance was preserved in the control group.

A method for correlative light microscopy (LM) and scanning electron microscopy (SEM) of human iliac crest bone biopsies

A method for correlative light microscopy (LM) and scanning electron microscopy (SEM) of human iliac crest bone biopsies

The Osteoporotic Syndrome: Detection, Prevention, and Treatment

With a steady increase in our aging population of which the majority are women, the osteoporotic-fracture syndrome is acquiring a sinister medical, social, and economic importance. This book on osteoporosis, written by eight eminent scholars in the field, is a timely and important contribution to a neglected subject. The distinguished contributors discuss the serious magnitude of the problem from epidemiologic and clinical points of view. They describe noninvasive methods for quantitating appendicular bone mass and trabecular bone mass, which are more sensitive than routine roentgenograms; the diagnostic use of iliac crest bone biopsies combined with the tetracycline fluorescence technique to visualize the newly deposited bone mineral; the care of the symptomatic menopausal patient; prevention of osteoporosis in young women; and management of the postmenopausal osteoporotic syndrome. The book is a delight to read because of its clear, crisp, easily understood language and adroit turns of phrase (eg, the facilitating effect

Bone scan appearances following biopsy of bone and bone marrow.

The influence of sternal marrow aspiration, iliac crest marrow aspiration, and iliac crest bone biopsy on bone scan appearances was examined. Eighteen patients were scanned a mean of 9.9 days after sternal marrow aspiration with a Salah needle (diameter 1.2 mm). Only one patient had an abnormality at the biopsy site. Bone scans obtained in 9 patients a mean of 10 days after iliac crest trephine marrow biopsy with a Jamshidi needle (diameter 3.5 mm) showed no abnormality at the biopsy site. In 18 patients with metabolic bone disease who had undergone iliac crest bone biopsy with an 8-mm needle, a scan abnormality due to the biopsy was usually present when the interval between the biopsy and the scan was 5 days to 2 months. Patients who were scanned within 3 days of iliac crest bone biopsy or more than 2 months after biopsy had normal scan appearance at the biopsy site.

Osteopenia with Normal Vitamin D Metabolites after Small-Bowel Resection for Crohn's Disease

Thirty-six unselected patients were investigated 3-24 years (mean, 7.8 years) after small-bowel resection for Crohn's disease (mean small intestinal resection, 105 cm). Iliac crest bone biopsies after in vivo tetracycline double-labelling showed a markedly reduced trabecular bone mass (controls, 0.25 +/- 0.06; patients, 0.15 +/- 0.05; p less than 0.01). The average bone remodeling and osteoid mineralization was normal, and only two patients demonstrated signs of frank but slight osteomalacia. The mean serum levels of the three vitamin D metabolites 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D, and 1,25-dihydroxyvitamin D were normal. The observed reduction in trabecular bone mass may theoretically be followed by an increased risk of spontaneous fractures.

Effect of propranolol treatment on bone mass, bone mineral content, bone remodelling, parathyroid function and vitamin D metabolism in hyperthyroidism.

The effect of propranolol 160-640 mg/day for 3 months on the accelerated loss of bone matrix and mineral in hyperthyroidism was studied in seventeen patients. A rise in serum thyroxine (P less than 0.01) during the first 3 weeks was followed by a fall (P less than 0.02). Serum triiodothyronine declined during the study (P less than 0.02). The enhanced bone mineral mobilization and collagen turnover continued during treatment and the bone mineral content decreased 3.2% (P less than 0.01). The secondary adaptive changes in serum parathyroid hormone and vitamin-D metabolites and in renal phosphate handling stayed unchanged. Iliac crest bone biopsies after tetracycline double-labelling showed initially a high bone turnover (P less than 0.01) with a reduced amount of cortical and trabecular bone (P less than 0.05). Following treatment bone formation rate decreased at both cellular and tissue level (P less than 0.01). No significant changes were observed in the amount of cortical and trabecular bone. The investigation shows that propranolol, in contrast to antithyroid medication, lacks any curative effect on the accelerated bone loss in hyperthyroidism.

Adult hypophosphatasia without apparent skeletal disease: "odontohypophosphatasia" in four heterozygote members of a family.

Twenty members of a family with adult hypophosphatasia were examined clinically and biochemically. Severe caries causing early loss of permanent teeth was the only clinical symptom which could be attributed to hypophosphatasia. None of them had a history of defective bone mineralization, rachitic skeletal alterations, and recurrent pseudofractures or fractures. An iliac crest bone biopsy of the proposita showed a normal finding corresponding to the age of the patient. Four family members in two subsequent generations were affected, thus suggesting an autosomal dominant inheritance. Their serum and leukocyte alkaline phosphatases were reduced. The phosphoethanolamine (PEA) excretion in the urine was increased to a level which suggests a heterozygote state. The serum alkaline phosphatase activity could be ascribed to the liver isoenzyme fraction. This was shown by polyacrylamide electrophoresis, by inhibition studies with organ-specific inhibitors, heat inactivation, inhibition by antibodies, and treatment with neuraminidase. The proposita had an unexplained, diffuse fatty infiltration of the liver. Thus, not only alterations of bone but also of liver metabolism in hypophosphatasia should be considered. The variety of adult hypophosphatasia described in this paper is characterized by the lack of severe bone abnormalities, the apparently autosomal dominant inheritance, and the reduction of bone and intestinal isoenzyme in the serum. Our study suggests that hypophosphatasia is a heterogeneous disorder which includes both severe and clinically mild forms.

Long-term calcitonin therapy in postmenopausal osteoporosis

Results are presented from a 2-year controlled study evaluating the efficacy of 100 units synthetic salmon calcitonin/d in the treatment of postmenopausal osteoporosis. All patients received 400 units D 2 po qd and 1200 mg CaCO 3 po qd. The 21 control and 24 treated patients (mean age 65) were not statistically different at baseline. Although mean total body calcium (TBCa) was not significantly different between treated and control patients throughout the study, mean differences in the change in TBCa from baseline (treated minus control) were significant at 12, 18, and 26 months. The mean slope of TBCa for treated patients, but not for controls, was significantly positive through 18 months. Iliac crest bone biopsies showed (1) a significantly greater percent total bone area in treated compared to control patients at 2 years, and (2) a significantly decreased percent resorbing surface in treated patients when evaluated by paired difference from baseline. At 4 months, serum calcium values were significantly lower in treated patients than in controls (mean difference, treated minus controls), but were not statistically different from controls at study completion. Urine calcium increased significantly for the first 4 months in treated subjects and then declined to baseline levels. Since urinary calcium increased, the increase in TBCa was probably associated with an increase in net intestinal calcium absorption.

Collagen Defect of Bone in Osteogenesis Imperfecta (Type I)

Osteogenesis imperfecta (OI) is an inherited disorder of connective tissue metabolism characterized by fragility of the bones, resulting in multiple fractures. In this study electron microscopic examination of the osteoid region of iliac crest bone biopsy specimens from a 55-year-old man and his three sons (18, 21, and 25 years of age) affected with the common Type I (autosomal dominant) form of OI revealed collagen fibrils consistently smaller in diameter than those from normal age-matched control subjects, with the majority of OI fibrils measuring 0.04-0.06 micron, as opposed to 0.06-0.08 micron in the control subjects. This defect may be due to the biosynthesis of Type III collagen, not normally found in adult lamellar bone or, more likely, to a failure of maturation of Type I fibrils to their normal diameters, possibly owing to the increased levels of hydroxylysine previously reported in OI collagen, a factor known to be inversely related to fibril diameter.