Inari S. Tamminen

Infrared spectroscopy indicates altered bone turnover and remodeling activity in renal osteodystrophy

Renal osteodystrophy alters metabolic activity and remodeling rate of bone and also may lead to different bone composition. The objective of this study was to characterize the composition of bone in high‐turnover renal osteodystrophy patients by means of Fourier transform infrared spectroscopic imaging (FTIRI). Iliac crest biopsies from healthy bone (n = 11) and patients with renal osteodystrophy (ROD, n = 11) were used in this study. The ROD samples were from patients with hyperparathyroid disease. By using FTIRI, phosphate‐to‐amide I ratio (mineral‐to‐matrix ratio), carbonate‐to‐phosphate ratio, and carbonate‐to‐amide I ratio (turnover rate/remodeling activity), as well as the collagen cross‐link ratio (collagen maturity), were quantified. Histomorphometric analyses were conducted for comparison. The ROD samples showed significantly lower carbonate‐to‐phosphate (p < .01) and carbonate‐to‐amide I (p < .001) ratios. The spatial variation across the trabeculae highlighted a significantly lower degree of mineralization (p < .05) at the edges of the trabeculae in the ROD samples than in normal bone. Statistically significant linear correlations were found between histomorphometric parameters related to bone‐remodeling activity and number of bone cells and FTIRI‐calculated parameters based on carbonate‐to‐phosphate and carbonate‐to‐amide I ratios. Hence the results suggested that FTIRI parameters related to carbonate may be indicative of turnover and remodeling rate of bone.

Longitudinal elastic properties and porosity of cortical bone tissue vary with age in human proximal femur

Tissue level structural and mechanical properties are important determinants of bone strength. As an individual ages, microstructural changes occur in bone, e.g., trabeculae and cortex become thinner and porosity increases. However, it is not known how the elastic properties of bone change during aging. Bone tissue may lose its elasticity and become more brittle and prone to fractures as it ages. In the present study the age-dependent variation in the spatial distributions of microstructural and microelastic properties of the human femoral neck and shaft were evaluated by using acoustic microscopy. Although these properties may not be directly measured in vivo, there is a major interest to investigate their relationships with the linear elastic measurements obtained by diagnostic ultrasound at the most severe fracture sites, e.g., the femoral neck. However, before the validity of novel in vivo techniques can be established, it is essential to understand the age-dependent variation in tissue elastic properties and porosity at different skeletal sites. A total of 42 transverse cross-sectional bone samples were obtained from the femoral neck (Fn) and proximal femoral shaft (Ps) of 21 men (mean±SD age 47.1±17.8, range 17-82years). Samples were quantitatively imaged using a scanning acoustic microscope (SAM) equipped with a 50MHz ultrasound transducer. Distributions of the elastic coefficient (c33) of cortical (Ct) and trabecular (Tr) tissues and microstructure of cortex (cortical thickness Ct.Th and porosity Ct.Po) were determined. Variations in c33 were observed with respect to tissue type (c33Trc33(Ct.Fn)=35.3GPa>c33(Tr.Ps)=33.8GPa>c33(Tr.Fn)=31.9GPa), and cadaver age (R(2)=0.28-0.46, p<0.05). Regional variations in porosity were found in the neck (superior 13.1%; inferior 6.1%; anterior 10.1%; posterior 8.6%) and in the shaft (medial 9.5%; lateral 7.7%; anterior 8.6%; posterior 12.0%). In conclusion, significant variations in elastic coefficients were detected between femoral neck and shaft as well as between the quadrants of the cross-sections of neck and shaft. Moreover, an age-related increase in cortical porosity and a stiffening of the bone tissue were observed. These findings may explain in part the increase in susceptibility to suffer low energy fractures during aging and highlight the potential of ultrasound in clinical osteoporosis diagnostics.

Bone biopsy findings and correlation with clinical, radiological, and biochemical parameters in children with fractures

In children the diagnosis of osteoporosis is based on fracture history and DXA‐derived BMD. Bone biopsy is an invasive but accurate method for studying bone characteristics. In this study we evaluated bone biopsy findings and their correlation with noninvasive measures of bone health. Transiliac bone biopsy was performed on 24 consecutive children (17 boys, median age 12 years, range 6 to 16 years) evaluated for suspected primary osteoporosis. Biopsy findings were compared with normative data and correlated with clinical, radiological, biochemical, and densitometric findings. The patients had sustained altogether 64 nonvertebral fractures (median 2.5) from low‐ or moderate‐energy traumas, and 14 patients (58%) had vertebral fractures. The median lumbar spine BMD Z‐score was −1.2 (range −3.1 to +1.0). Hypovitaminosis D was present in 58%. Histomorphometry showed low bone volume in 7 patients and normal bone volume in 17. Bone turnover was high in 7, low in 7, and normal in 10 patients. Histomorphometric findings correlated poorly with fracture history, serum bone turnover markers, and DXA findings. Vitamin D deficiency and low lumbar BMD were associated with high bone turnover in the biopsy. These findings underscore the difficulties in diagnosing pediatric osteoporosis. Bone histomorphometry gives additional information and may be useful when considering bisphosphonate treatment in children with suspected primary osteoporosis.

Altered bone composition in children with vertebral fracture.

Primary osteoporosis in children often leads to vertebral fractures, but it remains unknown whether these fractures associate with changes in bone composition. This study aimed to determine the differences in bone composition in fracture‐prone children with and without vertebral fractures, as assessed by Fourier transform infrared spectroscopic imaging (FTIRI) and bone histomorphometry. Iliac crest bone biopsies (n = 24) were obtained from children who were suspected of primary osteoporosis based on evidence from the fracture history and/or low bone mineral density (BMD) by dual‐energy X‐ray absorptiometry. Vertebral morphology was determined by radiography. Bone biopsies were analyzed using histomorphometry and FTIRI. Phosphate‐to‐amide I, carbonate‐to‐phosphate, carbonate‐to‐amide I, and cross‐link ratio (collagen maturity) were calculated. Children with (n = 14) and without (n = 10) vertebral fracture were compared. Low cancellous bone volume (BV/TV) was detected by histomorphometry in 36% of the children with vertebral fracture, and bone turnover rate was abnormal in 64% of them. Children with vertebral fractures had lower carbonate‐to‐phosphate ratios (p < .05) and higher collagen maturity (p < .05) than children without vertebral fracture. The children with low BV/TV in biopsy showed lower carbonate‐to‐amide I ratios (p < .05) than the children with normal bone volume. This study showed changes in bone composition among fracture‐prone children who had sustained a vertebral fracture. The observed changes in bone composition in these children may contribute to their greater propensity to sustain vertebral fractures.

Bilateral hip pain

In October, 2008, a 40-year-old man was referred to our hospital because of pain in his right groin, which had started a few days after he fell on his back at work 10 days earlier. He had mild asthma, which was treated with an occasional dose of inhaled broncholytics. On physical examination, he had right groin tenderness, and pain that was provoked by weight-bearing. A pelvic radiograph was normal. A tendon or muscle injury was suspected, and ultrasonography suggested a partial rupture of the rectus femoris muscle. MRI was planned as an elective outpatient procedure to rule out a total rupture of the tendon. A month after the onset of symptoms, the pain on weight bearing in the right groin had decreased but not resolved. He had also started to have pain in the left groin, and on examination, pain on rotation of both hip joints. MRI showed bilateral insuffi ciency fractures of the femoral necks (fi gure). Although he denied any regular recreational sports activities, his new job as a delivery-van driver required a lot of climbing. He had no dietary restrictions. Elderly relatives of our patient had a history of osteoporosis and osteopenia. Our patient was asked to restrict weight-bearing. A dual-energy x-ray absorptiometry scan showed that his bone mineral density was osteopenic at the lumbar spine and right femoral neck. The left femoral neck showed osteoporotic values (0·706 g/cm2; T score –2·8; Z score –2·4). Biochemistry tests for parathyroid and coeliac disease excluded secondary reasons for osteoporosis. His serum 25-hydroxyvitamin D(3) concentration was 33 nmol/L (normal > 40nmol/L). He was referred for iliac crest bone biopsy after tetracycline double-labelling. Low trabecular bone volume was found by histomorphometry (BV/TV 9·0%), and confi rmed by microcomputed tomography (9·9%). The turnover rate was normal as shown by normal amounts of formation and erosion surfaces (OV/BV 1·5%, OS/BS 14·2%, ES/BS 7·0%). The osteoblast and osteoclast surfaces were normal (Ob.S/BS 1·9%, Oc.S/BS 0·0%) as was the amount of mineralising surface (MS/BS 8·0%), but the mineral apposition rate was slightly low (0·28 μm/day). The results were consistent with normal-turnover osteoporosis. In a repeat MRI 10 weeks after the beginning of the symptoms bone oedema was diminished and in the follow up visit in March 2009, the fractures had clinically healed. His osteoporosis was treated with daily calcium 1000 mg, vitamin D 800 IU supplementation and weekly alendronate 70 mg. When last seen in June, 2010, he was asymptomatic. The diagnosis of insuffi ciency fracture of the femoral neck is commonly missed in clinical practice. The diagnostic algorithm should include, but not be restricted to radiographs. A normal radiograph does not rule out insuffi ciency fractures, as our patient’s case demonstrates. Osteoporosis may in itself be an aetiological factor in the case of insuffi ciency fractures. Long term bisphosphonate therapy has been linked with insuffi ciency fracturees in the femoral shaft. However, our patient’s fractures did not show features of such atypical fractures.Although secondary osteoporosis should be considered in young male patients, primary osteoporosis remains the diagnosis for up to half of patients. In the case of insuffi ciency fractures, the possibility of bilateral injury should be considered. Early diagnosis is warranted because untreated insuffi ciency fracture of the femoral neck can lead to a displaced fracture.