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Osteoporosis is a highly prevalent condition, characterized by compromised bone strength and fragility fractures and with an important associated socio-economic burden. Bisphosphonates are well established as the first line treatment for osteoporosis. However, while randomized control trials have in general demonstrated reasonable anti-fracture efficacy at the spine, they have shown moderate reduction in fracture incidence for non-vertebral sites. Furthermore, oral bisphosphonates are commonly associated with adverse gastrointestinal effects and both oral and parenteral bisphosphonates have been linked with osteonecrosis of the jaw and atypical femoral fracture, two rare but debilitating side effects. In addition, bisphosphonates are not recommended in patients with GFR <35 ml/min/1.73 m2. Hence, there is a clear requirement for newer agents, which are able to reduce fracture risk further, whilst overcoming the limitations of bisphosphonates. Over the past 20 years, knowledge and a deeper understanding of the various signalling pathways involved in bone remodelling has increased, enabling identification of additional targets for therapy. This review focuses on these newer therapies and includes anti-resorptive agents such as raloxifene and other selective oestrogen receptor modulators, the monoclonal antibody denosumab (which inhibits the RANKL pathway), odanacatib, a cathepsin K inhibitor and the anabolic agents, PTH analogue; PTH (1–34) and anti-sclerostin antibodies (activator of the Wnt pathway). Strontium ranelate will not be reviewed as recent reports highlight concerns surrounding its cardiovascular safety and together with an apparent increased risk of thrombosis, its future use remains uncertain. Some of these agents such as raloxifene, denosumab and teriparatide are already in clinical use whilst others are at varying stages of development. This review will provide an overview of the mechanisms of action of these therapeutic agents on the skeleton and assess their efficacy in osteoporosis and fracture prevention.

Corticosteroids have been the most widely used immunosuppressive agents since the first clinical transplantation in the 1950s. There are few studies of late steroid withdrawal in renal transplantation and none have prospectively assessed bone mineral density (BMD). The study aim was to assess the impact of corticosteroid withdrawal, in stable renal transplant recipients, on BMD and bone turnover.

Corticosteroids have been the most widely used immunosuppressive agents since the first clinical transplantation in the 1950s. There are few studies of late steroid withdrawal in renal transplantation and none have prospectively assessed bone mineral density (BMD). The study aim was to assess the impact of corticosteroid withdrawal, in stable renal transplant recipients, on BMD and bone turnover.

Quantitative studies of the kinetics of 99mTcmethylene diphosphonate 99mTcMDP in metabolic and metastatic bone disease require the measurement of free tracer in plasma to derive the input function. We describe a simple method of determination of free 99mTcMDP in vivobased on measurements of the ratio of the renal plasma clearances of total 99mTcMDP and 51Crethylenediaminetetraacetic acid 51CrEDTA. The method is based on evidence that free MDP is cleared through the kidneys by glomerular filtration. Measurements of the fraction of free 99mTcMDP were made between 0 and 4 h after injection in 70 postmenopausal women enrolled in a study of the effect of hormone replacement therapy on the wholeskeleton plasma clearance of 99mTcMDP Kbone. The glomerular filtration rate GFR was measured simultaneously from the plasma clearance of 51CrEDTA. The mean fractions and SD of free MDP measured were 0.757 0.050, 0.663 0.062, 0.550 0.052 and 0.472 0.053, respectively, at 17, 90, 150 and 210 min after injection. The results agreed closely with data using protein precipitation with trichloroacetic acid. Between 2 and 4 h after injection, the biological halflife of free 99mTcMDP in plasma was 92 min, compared with 540 min for bound MDP. Highly significant relationships were found between the fraction of free MDP measured in each patient at each of the four time points and the total plasma clearance of free 99mTcMDP KtotalGFRKbone, such that a larger value of Ktotalwas associated with a smaller fraction of free MDP. Multivariate regression analysis confirmed that this relationship held individually for both GFR and Kbone. A strong inverse relationship was found between Ktotaland the plasma concentration of free 99mTcMDP, but a much weaker relationship with the bound MDP concentration, a finding that is consistent with the slow reequilibration of bound MDP in the circulation. The results confirm that the fraction of free 99mTcMDP varies with time and shows significant differences between individuals, which are dependent on GFR and Kboneamongst other factors. © 2003 Lippincott Williams & Wilkins

Oestrogen inhibits bone resorption, at least in part, by regulating the production of several cytokines, including interleukin-6 (IL-6), IL-1, receptor activator of nuclear factor kappaB ligand (RANKL) and osteoprotegerin (OPG) by cells of the osteoblastic lineage. The selective oestrogen receptor modulator raloxifene (RAL) acts on bone in a similar manner to oestrogen, although the mechanisms of action of RAL on osteoblasts still remain unclear. We investigated and compared the effects of 17-beta oestradiol (E(2)) and RAL on the regulation of IL-6, IL-1, RANKL and OPG in vitro in primary human osteoblastic (HOB) cells and in an immortalised clonal human bone marrow stromal cell line (HCC1) with osteoblastic characteristics. We tested E(2) and RAL at concentrations ranging from 10(-12) to 10(-6) M. IL-6, IL-1alpha and IL-1beta, OPG and RANKL were measured by ELISA. RANKL and OPG mRNA steady state level was assessed by quantitative PCR analysis. Both E(2) and RAL led to a significant reduction in IL-6 production in the HOB cells, although the effect was more marked with E(2) (P<0.05). IL-1alpha and IL-1beta also decreased significantly following treatment with E(2) and RAL in the HCC1 cells (E(2) (10(-8), 10(-7) and 10(-6) M), % reduction (means+/-S.E.M.) compared with vehicle-treated cells - IL-1alpha: 84+/-7.4, 70.8+/-2.9*, 78.2+/-4.8*; IL-1beta: 79+/-10, 72.8+/-8.2*, 66.6+/-2.8*; RAL (10(-8), 10(-7) and 10(-6) M) - IL-1alpha: 72.4+/-5*, 79+/- 5.2*, 102+/-7.7; IL-1beta: 67.9+/-3.2*, 69+/-2.5*, 73.8+/- 6.2*; *P<0.05). OPG protein concentration decreased significantly in a dose-dependent manner following treatment with E(2) and RAL (% reduction E(2) (10(-8), 10(-7) and 10(-6) M) - HOB: 72.5+/-8.4*, 80+/-6.7*, 62.8+/-8.9*; HCC1: 109+/-4, 98.8+/-6, 54.5+/-3.4*; RAL (10(-8), 10(-7) and 10(-6) M) - HOB: 81.5+/-5.5*, 62.7+/-7.4*, 55.2+/-10.9*; HCC1: 92.7+/-7.4, 67+/-12.2*, 39+/-4.5*; *P<0.05). In the HCC1 cells, RANKL protein did not change significantly following E(2). In contrast, a significant reduction in RANKL was seen with RAL at 10(-7) and 10(-6) M (66+/-6.4% and 74+/-3% respectively). There was no change in OPG mRNA expression following E(2) or RAL in the HCC1 cells, although in the HOB cells we observed a significant reduction in OPG mRNA. RANKL mRNA decreased significantly in the HCC1 cells following RAL (10(-8), 10(-7)and 10(-6) M) treatment (% change from controls: 52+/-2*, 62+/-1*, 53+/-5.8*; *P<0.05). Similar results were seen in the HOB cells with RAL at 10(-6) M (RANKL mRNA: 72+/-5.5, P<0.05). In addition, there was a significant decrease in the RANKL/OPG ratio after RAL at 10(-6) M (HOB: 65.6+/-5*, HCC1: 56.9+/-20*; *P<0.05). RANKL/OPG ratio did not change significantly in the HCC1 cells following E(2). However, in contrast to RAL, we observed an increase in the RANKL/OPG ratio in the HOB cells following treatment with E(2). In conclusion, the study shows that RAL and E(2) have divergent cell-specific effects on the regulation of cytokines. The data also suggest that, in contrast to E(2), RAL may exert its anti-resorptive actions, at least in part, via the RANKL/OPG pathway. Further in vivo studies are required to confirm this.

Labeling of proteins with metallic radionuclides for use in radiopharmaceuticals involves covalently attaching a bifunctional chelator. In principle, use of smaller peptides allows this chelator to be incorporated during solid-phase peptide synthesis (SPPS) with total site specificity. To realize the advantages of this approach, a lysine−hynic conjugate Fmoc-N-ε-(Hynic-Boc)−Lys was synthesized for incorporating the well-known technetium-99m-binding hydrazinonicotinamide ligand into peptides during SPPS. It was used to synthesize a technetium-99m-labeled salmon calcitonin with the hynic-linked amino acid in place of lysine-18. A trifluoroacetate group protected the hynic during alkaline oxidation to the cyclic disulfide and was readily removed by mild acid treatment. The peptide was efficiently labeled (91−98% radiochemical yield) with Tc-99m in the presence of tricine and SnCl2 with high specific activity (>100 MBq/μg). The product showed good serum stability and specific affinity for human calcitonin receptors. Fmoc-N-ε-(Hynic-Boc)−Lys is a highly versatile technetium-binding amino acid for incorporation into peptides during SPPS. This allows total flexibility and control in the site of attachment and is suitable for a combinatorial approach to peptide radiopharmaceuticals.

Objectives: To assess the effects of tibolone 2.5 mg daily over a 10-year period on bone loss and other efficacy parameters in postmenopausal women, and to confirm its long-term safety and tolerability. Methods: A 10-year, open, non-randomized, prospective study was conducted in 110 postmenopausal women; 59 women received tibolone 2.5 mg daily and 51 were entered into an untreated control group. After 10 years, 31 women in the tibolone group (53%) and 26 (51%) in the control group remained in the study. Results: After 10 years, tibolone had significantly (p < 0.0001) increased the mean bone mineral density in the lumbar spine and femoral neck by 4.8% and 3.7%, respectively, compared with baseline. The corresponding changes in the control group were -8.5% and -8.9% (p < 0.0001 vs. baseline), respectively. The incidence and intensity of hot flushes were reduced in the tibolone group and there were improvements in vaginal cytology parameters. Tibolone was well tolerated. Conclusion: Tibolone 2.5 mg daily maintains its beneficial effects on bone loss over 10 years, while remaining well tolerated.

Reductions in circulating estradiol concentrations could be implicated in the pathogenesis of steroid-induced osteoporosis (SIOP) in men. We assessed serum estradiol and adrenal androgens (dehydroepiandrosterone sulfate [DHEAS] and androstenedione) in 77 men (group A: idiopathic osteoporosis [IOP], n = 38, aged [mean [plusmn] SD] 57.7 [plusmn] 12.1 years; group B: SIOP, n = 39, aged 55.3 [plusmn] 13.1 years). We also studied the relationship between bone mineral density (BMD) and serum estradiol in the group of men with SIOP. In group B, we observed a higher prevalence of low serum testosterone concentrations ([lt ]9.0 nmol/L) (P= .0052), which was significantly correlated with steroid dosage (r= [minus ]0.42, P= .0089) and estradiol concentrations (r= 0.42, P= .012). There was a significant positive association between BMD at the lumbar spine and serum estradiol (P= .004) in the men with SIOP (group B). A high proportion of subjects had low serum estradiol concentrations ([lt ]48 pmol/L) in both groups (group A: 44.7 %, group B: 36 %). Serum adrenal androgens concentrations were also significantly suppressed in group B (serum androstenedione[mdash ]group A: 4.99 [plusmn] 1.8; Group B: 2.1 [plusmn] 1.6 nmol/L; P= .0001). Serum DHEAS was undetectable in 59% of patients in group B versus 6% in group A (P= .001). Reductions in androstenedione also correlated with steroid dosage (r= [minus ]0.35, P= .01). In conclusion, the data show that adrenal androgens synthesis is markedly suppressed in men with SIOP. The clinical relevance of this finding remains to be determined. This study also shows a positive association between serum estradiol and BMD and a high prevalence of low serum estradiol in men with SIOP. Low serum estradiol may contribute to bone loss in men with SIOP.

The purpose of this study was to quantify indices of regional bone metabolism in Paget's disease and to compare these indices with normal bone using dynamic18F‐fluoride positron emission tomography (PET). Seven patients with vertebral Paget's disease had 1 h dynamic18F‐fluoride PET scans performed. The scans included a diseased vertebra and an adjacent normal vertebra. Arterial plasma input functions were also measured. A three‐compartment, four‐parameter model was used with nonlinear regression analysis to estimate bone kinetic variables. Compared with normal bone, pagetic bone demonstrated higher values of plasma clearance to bone mineral (Ki; 1.03 × 10−1vs. 0.36 × 10−1ml/min per milliliter; p= 0.018) and clearance to total bone tissue (K1; 2.38 × 10−1vs. 1.25 × 10−1ml/min per milliliter; p= 0.018), reflecting increased mineralization and blood flow, respectively. Release of18F‐fluoride from bone mineral (k4) was lower in pagetic bone (p= 0.022), suggesting tighter binding of18F‐fluoride to bone mineral. The notional volume of the extravascular bone compartment (K1/k2) was greater in pagetic bone (p= 0.018). Although the unidirectional extraction efficiency from the extravascular space to bone mineral (Ki/K1) was greater in pagetic bone (p= 0.018), a lower pagetic value of k2(p= 0.028), describing the rate of transfer from the bone extravascular compartment to plasma, suggests that the18F‐fluoride that enters the relatively fibrotic marrow space of pagetic bone may be less accessible for return to plasma. These findings confirm some of the known pathophysiology of Paget's disease, introduce some new observations, and show how dynamic18F‐fluoride PET may be of value in the measurement of regional metabolic parameters in focal bone disorders.

The purpose of this study was to quantify indices of regional bone metabolism in Paget's disease and to compare these indices with normal bone using dynamic18F‐fluoride positron emission tomography (PET). Seven patients with vertebral Paget's disease had 1 h dynamic18F‐fluoride PET scans performed. The scans included a diseased vertebra and an adjacent normal vertebra. Arterial plasma input functions were also measured. A three‐compartment, four‐parameter model was used with nonlinear regression analysis to estimate bone kinetic variables. Compared with normal bone, pagetic bone demonstrated higher values of plasma clearance to bone mineral (Ki; 1.03 × 10−1vs. 0.36 × 10−1ml/min per milliliter; p= 0.018) and clearance to total bone tissue (K1; 2.38 × 10−1vs. 1.25 × 10−1ml/min per milliliter; p= 0.018), reflecting increased mineralization and blood flow, respectively. Release of18F‐fluoride from bone mineral (k4) was lower in pagetic bone (p= 0.022), suggesting tighter binding of18F‐fluoride to bone mineral. The notional volume of the extravascular bone compartment (K1/k2) was greater in pagetic bone (p= 0.018). Although the unidirectional extraction efficiency from the extravascular space to bone mineral (Ki/K1) was greater in pagetic bone (p= 0.018), a lower pagetic value of k2(p= 0.028), describing the rate of transfer from the bone extravascular compartment to plasma, suggests that the18F‐fluoride that enters the relatively fibrotic marrow space of pagetic bone may be less accessible for return to plasma. These findings confirm some of the known pathophysiology of Paget's disease, introduce some new observations, and show how dynamic18F‐fluoride PET may be of value in the measurement of regional metabolic parameters in focal bone disorders.

The burden of non‐vertebral fractures is enormous. Hip fractures account for nearly 10% of all fractures (and a much greater proportion in the elderly), while wrist fractures may account for up to 23% of all limb fractures. The best available predictors of non‐vertebral fracture risk are low BMD and a tendency to fall. Hip, forearm, proximal humerus and rib fractures have all been associated with low BMD, though ankle fracture is not strongly related to osteoporosis. Although clinical risk factors identify only about one‐third of postmenopausal women at increased risk of osteoporotic fracture, the occurrence of one fracture commonly predicts a second fracture. Guidelines are presented for identifying and treating patients at risk of non‐vertebral osteoporotic fractures, especially those with a previous fracture, based on the algorithm recently published by the Royal College of Physicians and the Bone and Tooth Society. Prevention of falls and use of external hip protectors may reduce the occurrence of hip fracture. Treatment options for patients presenting with hip fracture include HRT, bisphosphonates, and calcium plus vitamin D, and for Colles' fracture include general measures, HRT, bisphosphonates, or calcitonin plus calcium.

The burden of non‐vertebral fractures is enormous. Hip fractures account for nearly 10% of all fractures (and a much greater proportion in the elderly), while wrist fractures may account for up to 23% of all limb fractures. The best available predictors of non‐vertebral fracture risk are low BMD and a tendency to fall. Hip, forearm, proximal humerus and rib fractures have all been associated with low BMD, though ankle fracture is not strongly related to osteoporosis. Although clinical risk factors identify only about one‐third of postmenopausal women at increased risk of osteoporotic fracture, the occurrence of one fracture commonly predicts a second fracture. Guidelines are presented for identifying and treating patients at risk of non‐vertebral osteoporotic fractures, especially those with a previous fracture, based on the algorithm recently published by the Royal College of Physicians and the Bone and Tooth Society. Prevention of falls and use of external hip protectors may reduce the occurrence of hip fracture. Treatment options for patients presenting with hip fracture include HRT, bisphosphonates, and calcium plus vitamin D, and for Colles' fracture include general measures, HRT, bisphosphonates, or calcitonin plus calcium.

We report a study of the renal and whole-blood kinetics of 18F-fluoride and 99mTc-methylene diphosphonate (99mTc-MDP) and their effect on the evaluation of the skeletal kinetics of the two bone tracers. Data were obtained during an investigation of postmenopausal women taking hormone replacement therapy who were compared with untreated, age-matched controls. After intravenous injection of 18F-fluoride (1 MBq), 99mTc-MDP (1 MBq), 51Cr-ethylenediaminetetraacetic acid (51Cr-EDTA) (3 MBq) and 125I-human serum albumin (125I-HSA) (0.25 MBq), multiple blood samples and urine collections were taken between 0 and 4 h after injection. 51Cr-EDTA data were used to evaluate the glomerular filtration rate (GFR) and the completeness of each timed urine collection. 125I-HSA data were used to evaluate the plasma volume and the red cell uptake of the other three tracers. At 4 h, the cumulative urine excretions (and standard deviations, SDs) were: 99mTc-MDP, 58.2 (4.8); 18F-fluoride, 36.1 (5.7); 51Cr-EDTA, 81.5 (4.5). Plots of the renal clearance of 18F-fluoride against urine volume showed that urine flow rates greater than 5 ml·min−1were necessary to ensure a constant renal clearance of 18F and hence stable conditions for the evaluation of bone tracer kinetics. In contrast, a low urine flow rate had no effect on the renal kinetics of 99mTc-MDP. For MDP, the evaluation of skeletal kinetics requires data on protein binding so that calculations can be performed for free MDP. In the present study, protein binding of MDP was evaluated from the ratio of total 99mTc-MDP renal clearance to GFR based on the principle that free 99mTc-MDP is a GFR tracer. Between 0 and 4 h after injection, the fractional protein binding of MDP increased linearly with time, changing from 21±5 immediately after injection to 58±5 at 4 h. Although red cell uptake of 99mTc-MDP was negligible, for 18F-fluoride around 30 of circulating tracer was transported in red cells. In view of the data showing the rapid transport of 18F-fluoride across the red cell membrane, bone kinetic data for 18F are more accurately reported as whole-blood clearance rather than plasma clearance.

In recent years, the range of treatments available for patients with osteoporosis has greatly increased. A decade ago, the only proven therapy was estrogen, but today the choices include bisphosphonates, selective estrogen-receptor modulators, calcitonin, and parathyroid hormone. Clinical trials involving bone mineral density (BMD) scans of the spine and femur have had an important role in the evaluation of these new therapies. In particular, the efficacy of treatments has now been verified in large studies powered to show reductions in fracture risk. In contrast with the use of BMD scans in research studies, their value for monitoring response to treatment in individual patients is less certain. In many cases, the increases in BMD are too small to reliably distinguish between true changes and measurement error. However, experience with estrogen and bisphosphonates suggests that these treatments have a beneficial effect on bone in most patients. Follow-up scans for patients taking these agents are therefore of limited value, apart from offering reassurance to the patient and the doctor. However, when new therapies are first introduced, follow-up scans have a useful role in building up the physician's experience and confidence.

The nuclear medicine bone scan has historically been one of the most common investigations to stage and monitor skeletal malignancy. Current guidelines for using radiographs to assess the response of skeletal metastases to systemic therapy are limited in their ability to give a timely results. Despite some minor limitations caused by the flare phenomenon, skeletal scintigraphy remains widely used for this purpose, both clinically and in trials of new cancer treatments. Nuclear medicine has also played an important role in the posttherapy evaluation of primary bone tumors, both with bone agents and nonspecific tumor agents, such as ^2^0^1TI. In the future, it is possible that positron emission tomography radiopharmaceuticals such as 18F-fluorodeoxyglucose may prove to be superior in predicting and measuring treatment response in primary and metastatic bone and bone marrow disease, but further work is required in this area.

Morphometric X-ray absorptiometry (MXA) has recently been developed to assess vertebral deformity status using dual energy X-ray absorptiometry (DXA) machines. In contrast to bone densitometry, a vertebral morphometry phantom is not supplied by any machine manufacturer. The aim of this study was to develop a suitable phantom to quantify the accuracy and precision of the vertebral measurement software on three DXA scanners in vitroand to perform a weekly quality control (QC) scan over a 30-month period to evaluate any drift or changes in measurement accuracy over time. The phantom was constructed from Perspex and aluminium to simulate soft tissue and bone, respectively. 13 aluminium rectangles (each 30 mm wide, 25 mm high and 3 mm thick, with edges (“endplates”) 6 mm thick) were set into one side of a solid Perspex block to represent the vertebral bodies from the fourth thoracic (T4) to the fourth lumbar (L4). The phantom was scanned on both the Hologic QDR2000plusand the QDR-4500A as well as the Lunar Expert-XL. Three consecutive lateral MXA scans were acquired on the Hologic machines using each of the scan modes available. On the QDR-2000plus, the lateral scan modes available are fast, array and high definition, which are all dual energy modes. These three scan modes are also available on the QDR-4500A, with the addition of a single energy scan mode. Four lateral scans were acquired on the Expert-XL machine using the single scan mode available. Each MXA scan was analysed twice by a trained operator using the standard software supplied by each manufacturer. A QC scan was performed approximately weekly over a 30-month period on only the QDR-4500A machine, and total phantom height was measured from the inferior edge of L4 to the superior edge of T4. Accuracy of “vertebral” height measurement varied between the three DXA machines and between the scan modes available. All underestimated “true” vertebral height by between 0.4% and 8.6%, with the scan modes using finer collimation producing the most accurate results. Repeat analysis precision of vertebral height measurement was best on the QDR-4500A, followed by the Expert-XL, and was poorest on the QDR-2000plus. The QC scans acquired on the QDR-4500A suggested that it was a highly stable machine, little affected by even major repairs. It must be remembered that these in vitrophantom results may not be representative of the true in vivosituation. The MXA phantom appears to be a useful tool for documenting the stability of the mechanical instruments and for checking the long-term consistency of operator precision.

Because resources do not allow all women to be screened for osteoporosis, clinical risk factors are often used to identify those individuals at increased risk of fracture who are then assessed by bone densitometry. The aim of this study was to compare calcaneal quantitative ultrasound (QUS) and axial bone mineral density (BMD) T and Z scores in a large group of women, some with no clinical risk factors and others with one or more risk factors for osteoporosis. The study population consisted of 1115 pre‐ and postmenopausal women. A subgroup of 530 women was used to construct reference data for calculating T and Z scores. A total of 786 women was found to have one or more of the following risk factors: (i) atraumatic fracture since the age of 25 years, (ii) report of X‐ray osteopenia, (iii) predisposing medical condition or use of therapy known to affect bone metabolism, (iv) premature menopause before the age of 45 years or a history of amenorrhea of longer than 6 months duration, (v) family history of osteoporosis, (vi) body mass index (BMI) <20 kg/m2, and (vii) current smoking habit. Calcaneal broadband ultrasound attenuation (BUA) and speed of sound (SOS) measurements were performed on a Hologic Sahara and a DTUone and BMD was measured at the spine and hip using dual‐energy X‐ray absorptiometry (DXA). The Z score decrements associated with the seven risk factors calculated using multivariate regression analysis were similar for QUS and BMD measurements. Z score decrements (mean of BMD and QUS measurements combined) associated with a history of atraumatic fracture (−0.67), X‐ray osteopenia (−0.36), a family history of osteoporosis (−0.23), and a low BMI (−0.53) were all statistically significant compared with women with no risk factors. Z score decrements associated with a medical condition or use of therapy known to affect bone metabolism, a premature menopause or prolonged amenorrhea, or those who were current smokers were not significantly different from zero. As the number of risk factors present in each individual increased, the mean Z score decrements became more negative, increasing from −0.28 for women with one risk factor to −1.19 for those with four or more risk factors. QUS and BMD measurements yielded similar mean Z scores for women with one, two, three, or more than four risk factors. Using the World Health Organization (WHO) criteria to diagnose osteoporosis for BMD measurements and revised diagnostic criteria for QUS, approximately one‐third of postmenopausal women aged 50+ years with clinical risk factors were classified as osteoporotic compared with only 12% of women without clinical risk factors. Over two‐thirds of postmenopausal women with risk factors were classified as osteopenic or osteoporotic and approximately 28% were classified as normal. The proportion of women classified into each diagnostic category was similar for BMD and QUS. In conclusion, clinical risk factors for osteoporosis affected calcaneal BUA and SOS Z score measurements to the same extent as axial BMD Z score measurements. Provided revised diagnostic criteria are adopted for QUS, similar proportions of postmenopausal women are identified as osteopenic or osteoporotic as with BMD.

Because resources do not allow all women to be screened for osteoporosis, clinical risk factors are often used to identify those individuals at increased risk of fracture who are then assessed by bone densitometry. The aim of this study was to compare calcaneal quantitative ultrasound (QUS) and axial bone mineral density (BMD) T and Z scores in a large group of women, some with no clinical risk factors and others with one or more risk factors for osteoporosis. The study population consisted of 1115 pre‐ and postmenopausal women. A subgroup of 530 women was used to construct reference data for calculating T and Z scores. A total of 786 women was found to have one or more of the following risk factors: (i) atraumatic fracture since the age of 25 years, (ii) report of X‐ray osteopenia, (iii) predisposing medical condition or use of therapy known to affect bone metabolism, (iv) premature menopause before the age of 45 years or a history of amenorrhea of longer than 6 months duration, (v) family history of osteoporosis, (vi) body mass index (BMI) <20 kg/m2, and (vii) current smoking habit. Calcaneal broadband ultrasound attenuation (BUA) and speed of sound (SOS) measurements were performed on a Hologic Sahara and a DTUone and BMD was measured at the spine and hip using dual‐energy X‐ray absorptiometry (DXA). The Z score decrements associated with the seven risk factors calculated using multivariate regression analysis were similar for QUS and BMD measurements. Z score decrements (mean of BMD and QUS measurements combined) associated with a history of atraumatic fracture (−0.67), X‐ray osteopenia (−0.36), a family history of osteoporosis (−0.23), and a low BMI (−0.53) were all statistically significant compared with women with no risk factors. Z score decrements associated with a medical condition or use of therapy known to affect bone metabolism, a premature menopause or prolonged amenorrhea, or those who were current smokers were not significantly different from zero. As the number of risk factors present in each individual increased, the mean Z score decrements became more negative, increasing from −0.28 for women with one risk factor to −1.19 for those with four or more risk factors. QUS and BMD measurements yielded similar mean Z scores for women with one, two, three, or more than four risk factors. Using the World Health Organization (WHO) criteria to diagnose osteoporosis for BMD measurements and revised diagnostic criteria for QUS, approximately one‐third of postmenopausal women aged 50+ years with clinical risk factors were classified as osteoporotic compared with only 12% of women without clinical risk factors. Over two‐thirds of postmenopausal women with risk factors were classified as osteopenic or osteoporotic and approximately 28% were classified as normal. The proportion of women classified into each diagnostic category was similar for BMD and QUS. In conclusion, clinical risk factors for osteoporosis affected calcaneal BUA and SOS Z score measurements to the same extent as axial BMD Z score measurements. Provided revised diagnostic criteria are adopted for QUS, similar proportions of postmenopausal women are identified as osteopenic or osteoporotic as with BMD.

Over the past decade, bone density scanning has come to be seen as an essential part of the evaluation of patients at risk of osteoporosis. Although dual x-ray absorptiometry (DXA) is the technique most associated with the recent growth in bone densitometry, several innovative devices for performing measurements at sites in the peripheral skeleton are also available. This article examines the question of whether there is any one method or measurement site that performs better than all the others at identifying patients at risk of fracture. Given that it is essential to make greater use of the small, low-cost peripheral devices if the many millions of women most at risk are to be identified and treated, what approaches to the interpretation of bone density scans can be adopted to ensure the greatest degree of consistency among different methods? Finally, does it matter if the imperfect correlation among different types of measurement results in different patients being selected for treatment on the basis of different techniques?

The role of positron emission tomography (PET) in the evaluation and management of skeletal disorders is increasing. A number of reports are available in both benign and malignant disease with a variety of tracers. The bone agent ^1^8F-fluoride can be used to evaluate bone metastases both qualitatively and, for a number of focal and systemic skeletal disorders, quantitatively. 18-Fluorodeoxyglucose is used as a tumor agent in both primary and metastatic bone and bone marrow malignancies; its use has also been described in the evaluation of infection within the skeleton. A possible role for the use of the hypoxia selective tracer ^1^8F-fluoromisonidazole in skeletal infection also exists. This article summarizes the current role of PET in the skeleton with regard to these tracers and diseases.

This article discusses methods for quantifying bone turnover based on tracer kinetic studies of the short-lived radiopharmaceuticals ^9^9^mTc-MDP and ^1^8F-fluoride. Measurements of skeletal clearance obtained by using these tracers reflect the combined effects of skeletal blood flow and osteoblastic activity. The pharmacokinetics of each tracer is described, together with some of the quantitative tests of skeletal function that have been described in the literature. The physiologic interpretation of quantitative measurements of bone obtained with the use of short half-life radionuclides is discussed, and the advantages and limitations of ^9^9^mTc-MDP and ^1^8F-fluoride are compared and contrasted. Currently, ^1^8F-fluoride dynamic positron emission tomography (PET) is the technique of choice for physiologically precise quantitative studies of bone. However, comparable data could probably be obtained by using ^9^9^mTc-MDP if methods for single photon emission computed tomography (SPECT) quantitation were improved.

Prevalent vertebral deformities are associated with a substantially increased risk of subsequent vertebral and nonvertebral fractures. Knowledge of vertebral fracture status is an important component in the prediction of further fractures in patients with osteoporosis. This study reports a comparison of the quantitative identification of vertebral deformities on morphometric X‐ray absorptiometry (MXA) scans and conventional radiographs (MRX) in 161 postmenopausal women (mean age ± SD, 64 ± 7.1 years) recruited from patients referred by their family doctor for bone density measurement (n= 119) and osteoporotic subjects with known vertebral deformities attending an osteoporosis clinic (n= 42). Each subject had MXA scans and MRXs of the thoracolumbar spine, to image the vertebrae from T4–L4, at a single visit. The scans and radiographs were analyzed by two trained observers using six points to quantify the shape of each vertebral body. From these points, three vertebral heights were measured: anterior, middle, and posterior. Vertebral deformities were identified using the algorithms proposed by Eastell and by McCloskey. Generally good to excellent agreement (per vertebra, κ = 0.87–0.93; per subject, κ = 0.81–0.91) was observed between the two algorithms used for quantitative vertebral deformity identification using MXA or MRX More moderate agreement (per vertebra, κ = 0.70–0.79; per subject, κ = 0.67–0.75) was seen when comparing the same algorithm between MXA and MRX Agreement between MXA and MRX for the McCloskey algorithm was better than for the Eastell algorithm, largely because of the lower number of false positives produced by the McCloskey methodology. Deformity identification by MXA was limited because of poor image quality, primarily in the upper thoracic spine. One in six MRX deformities were missed by MXA as they occurred in vertebrae not visualized sufficiently for analysis on the MXA scans. Deformity identification was poorer in the upper thoracic spine in analyzable vertebrae with a sensitivity of 50.0% for MXA in terms of MRX using the Eastell algorithm for the vertebral levels T4–T7, compared with 80.6% for L1–L4. MXA proved to be more effective at identifying moderate to severe MRX deformities producing a sensitivity of 22.0% for MXA in terms of identifying MRX grade 1 deformities using the Eastell algorithm, compared with 81.6% for grade 2 deformities. Although MXA image quality is inferior to that of conventional radiographs, MXA has distinct advantages such as a substantially reduced effective dose to the patient and acquisition of a single image of the spine. MXA is a potentially useful, relatively fast, low‐radiation technique to identify prevalent vertebral deformities, particularly moderate to severe deformities in the middle/lower thoracic and lumbar spine, in conjunction with morphometric radiography in some patients.

Prevalent vertebral deformities are associated with a substantially increased risk of subsequent vertebral and nonvertebral fractures. Knowledge of vertebral fracture status is an important component in the prediction of further fractures in patients with osteoporosis. This study reports a comparison of the quantitative identification of vertebral deformities on morphometric X‐ray absorptiometry (MXA) scans and conventional radiographs (MRX) in 161 postmenopausal women (mean age ± SD, 64 ± 7.1 years) recruited from patients referred by their family doctor for bone density measurement (n= 119) and osteoporotic subjects with known vertebral deformities attending an osteoporosis clinic (n= 42). Each subject had MXA scans and MRXs of the thoracolumbar spine, to image the vertebrae from T4–L4, at a single visit. The scans and radiographs were analyzed by two trained observers using six points to quantify the shape of each vertebral body. From these points, three vertebral heights were measured: anterior, middle, and posterior. Vertebral deformities were identified using the algorithms proposed by Eastell and by McCloskey. Generally good to excellent agreement (per vertebra, κ = 0.87–0.93; per subject, κ = 0.81–0.91) was observed between the two algorithms used for quantitative vertebral deformity identification using MXA or MRX More moderate agreement (per vertebra, κ = 0.70–0.79; per subject, κ = 0.67–0.75) was seen when comparing the same algorithm between MXA and MRX Agreement between MXA and MRX for the McCloskey algorithm was better than for the Eastell algorithm, largely because of the lower number of false positives produced by the McCloskey methodology. Deformity identification by MXA was limited because of poor image quality, primarily in the upper thoracic spine. One in six MRX deformities were missed by MXA as they occurred in vertebrae not visualized sufficiently for analysis on the MXA scans. Deformity identification was poorer in the upper thoracic spine in analyzable vertebrae with a sensitivity of 50.0% for MXA in terms of MRX using the Eastell algorithm for the vertebral levels T4–T7, compared with 80.6% for L1–L4. MXA proved to be more effective at identifying moderate to severe MRX deformities producing a sensitivity of 22.0% for MXA in terms of identifying MRX grade 1 deformities using the Eastell algorithm, compared with 81.6% for grade 2 deformities. Although MXA image quality is inferior to that of conventional radiographs, MXA has distinct advantages such as a substantially reduced effective dose to the patient and acquisition of a single image of the spine. MXA is a potentially useful, relatively fast, low‐radiation technique to identify prevalent vertebral deformities, particularly moderate to severe deformities in the middle/lower thoracic and lumbar spine, in conjunction with morphometric radiography in some patients.

Abstract:: The aim of this study was to assess a dry calcaneal quantitative ultrasound (QUS) device by examining: (i) short- and long-term precision; (ii) the ability of the ultrasound parameters to identify women with vertebral fractures; (iii) age- and menopause-related bone loss; (iv) applicability of the WHO criteria in scan interpretation. The study group consisted of 422 healthy women with no risk factors associated with osteoporosis (227 premenopausal and 195 postmenopausal) and 93 women with one or more vertebral fractures. All women had calcaneal QUS and bone mineral density (BMD) measurements of the lumbar spine and hip performed. Broadband ultrasound attenuation (BUA) and speed of sound (SOS) measurements in the heel were combined and expressed as estimated heel BMD. Short-term precision studies yielded coefficient of variations of 0.3% for SOS, 4% for BUA and 3.3% for estimated heel BMD. Standardized short-term precision values were approximately 0.2 SD. Long-term standardized precision errors ranged from 0.17 to 0.38 SD. All the QUS and BMD measurement parameters showed significant negative relationships with age in the postmenopausal group. Annual losses were 0.35 dB/MHz per year for BUA, 0.56 m/s per year for SOS and 0.002 g/cm2 per year for estimated heel BMD. All the QUS and BMD parameters were able to discriminate between healthy postmenopausal women and women with vertebral fracture. Age-adjusted odds ratios for each SD decline in QUS measurements were 3.63, 5.25 and 4.79 for BUA, SOS and estimated heel BMD respectively. Corresponding odds ratios for BMD at the lumbar spine, femoral neck and total hip were 2.39, 2.51 and 2.95 respectively. When the QUS and BMD parameters were expressed as T-scores, estimated heel BMD showed the least age-related decline, while femoral neck BMD displayed the greatest decrease with age. The mean T-score and prevalence of osteoporosis (T<−2.5) for a Caucasian woman aged 60–65 years were −1.35 and 21% respectively for the lumbar spine compared with −0.59 and 2% for estimated heel BMD. In conclusion, this study revealed that contact ultrasound can detect age- and menopause-related influences on bone status and was able to discriminate between healthy individuals and women with vertebral fracture. However, the widely accepted threshold of a T-score of less than −2.5 for the definition of osteoporosis may need modifying for the interpretation of QUS scans.

Breast cancer is a disease that commonly metastasizes to bone, increasing morbidity, mortality, and health service costs. The 99m technetium (^9^9^mTc) diphosphonate bone scan historically has played a significant part in the evaluation of skeletal disease and continues to be one of the most clinically utilized investigations in the staging and follow up of breast cancer patients. More tumor-specific radiopharmaceuticals are now being evaluated and, in particular, 18-fluoro-2-deoxyglucose positron emission tomography (^1^8FDG PET) may have a greater role in this disease in the future.

Abstract:: Morphometric techniques, which use conventional lateral spine radiographs to quantify vertebral body shape (morphometric radiography, MRX), have proved a useful tool in the identification and evaluation of osteoporotic vertebral deformities. Recently a new method of acquiring the images required for vertebral morphometry using dual-energy X-ray absorptiometry scanners (morphometric X-ray absorptiometry, MXA) has been developed. In this study we compare repeat analysis precision of vertebral height measurement using MXA and MRX. Twenty-four postmenopausal women were recruited (mean age 67 + 5.8 years): 12 normal subjects and 12 with osteoporosis and vertebral deformities. Each subject had a MXA scan and lateral thoracic and lumbar radiographs at a single appointment, which were each analyzed quantitatively in a masked fashion, using a standard 6-point method, twice by one observer and once by a second observer. Anterior (Ha), mid (Hm) and posterior (Hp) vertebral heights were measured and wedge (Ha/Hp) and mid-wedge (Hm/Hp) ratios calculated for each vertebral body. Intra- and interobserver precision were consistently poorer in MXA compared with MRX in both normal subjects and those with vertebral deformities, with MXA CV% generally at least 50% higher than corresponding values for MRX. For both MXA and MRX interobserver precision was clearly poorer than intraobserver precision, a problem associated with any morphometric technique. MXA intra- and interobserver precision were significantly poorer for subjects with vertebral deformities compared with those without, with a CV% for deformity subjects up to twice that of normal subjects. Conversely, MRX showed little or no obvious worsening of intra- or interobserver precision for deformity subjects. Comparison of MXA precision in the normal and deformed vertebrae of the deformity subjects demonstrated that the poorer precision in these subjects compared with normal subjects was the result of increased variability in point placement on the deformed vertebrae themselves. However, the precision for normal vertebrae in these subjects was also somewhat poorer than the precision in normal subjects. We conclude that MXA precision is generally poorer than that of MRX and that the presence of vertebral deformities has a more pronounced effect on MXA precision than on MRX precision.

Abstract:: Since its commercial introduction a decade ago, the technique of dual-energy X-ray absorptiometry (DXA) has been widely recognized as a useful and sensitive method of measuring changes in bone mineral density (BMD) at selected sites in the skeleton such as the spine and proximal femur. Because of their high precision and stable calibration, DXA scanners are frequently used in clinical trials to evaluate new treatments for osteoporosis. Quality assurance procedures based on regular scanning of phantoms are widely adopted in such trials, and continuity of the phantom BMD measurements is generally believed to ensure continuity in the in-vivo calibration. We report a change in calibration of a DXA scanner that occurred during a clinical trial where the calibration shift was different for the spine and femur sites and was not predicted or explained by the standard quality control procedures using phantoms. However, we show that provided patients enrolled in studies are thoroughly randomized and the statistical analysis is confined to the differences between the treated and control groups, then the effects of such calibration shifts on conclusions regarding the efficacy of treatment are considerably smaller than the random statistical errors.

Seventy-five women with clinical stage I or stage II carcinoma of the breast have had radionuclide bone scans at the time of presentation and at 6-monthly intervals during a mean follow-up period of 39 months. Patients with evidence of metastases on bone scan, either at the time of presentation or during follow-up, had significantly higher mortality and morbidity rates than those with persistently negative scans.Whatever the clinical stage, breast cancer patients with a positive bone scan have a very poor short term prognosis and local therapy to the breast is inadequate. A plan is outlined which incorporates the patient's bone scan status into the decision to introduce endocrine therapy or chemotherapy.

Summary Measurements of broadband ultrasonic attenuation (BUA) and velocity of ultrasound through the heel (heel velocity, HV) were performed with a Contact Ultrasonic Bone Analyzer (CUBA-Research model) in 229 women. The subjects consisted of 16 healthy young volunteers (Group 1, mean age 26 years), 170 healthy pre- and postmenopausal women (Group 2, mean age 53 years), and 43 osteoporotic women with radiographically defined vertebral crush fracture (Group 3, mean age 66 years). Subjects in Group 1 had 10 repeated measurements in a study of short-term precision. Women in Groups 2 and 3 also had dual X-ray absorptiometry (DXA) scans to measure lumbar spine and femoral neck bone mineral density (BMD). The BUA and HV measurements for all 229 women showed a significant correlation (r = 0.75,P < 0.001). The precision study on the subjects in Group 1 gave a root mean square coefficient of variation of 6.3% for BUA and 1.04% for HV. Linear regression analysis gave the following relationship between BUA and age for the 170 normal women in Group 2: BUA = 83.6 - 0.86 (age 40) dB/MHz (r = -0.31,P < 0.001, SEE = 16.3 dB/MHz). The relationship between HV and age was as follows: HV = 1614 - 2.3 (age 40) m/s (r = -0.33,P < 0.001, SEE = 42 m/s). Multivariate regression analysis showed that in addition to age, years since the menopause was also a significant factor in determining both BUA and HV. In the first 5 years following the menopause, BUA and HV decreased by 2.2% and 0.3%/year, respectively, whereas in the next 10 years the rates of decrease fell to 0.5% and 0.03%/year. The BUA and HV measurements on the 43 osteoporotic subjects in Group 3 gave mean T-scores of -2.1 and -1.9 compared with 59 premenopausal women, and mean Z-scores of -1.3 and -0.9 compared with 26 age-matched normal women in Group 2, respectively. In comparison, the lumbar spine and femoral neck DXA measurements in the same subjects gave mean T-scores of -2.9 and -2.1 and mean Z-scores of -1.7 and -1.0, respectively. Lumbar spine BMD gave the best discrimination between women with osteoporotic vertebral fractures and normal subjects. However, the difference between the lumbar spine and BUA Z-scores was not statistically significant. Femoral neck BMD was equivalent to the ultrasound parameters in T-score and Z-score values.

Summary: Bone mineral density (BMD) at the lumbar spine, femoral neck, trochanteric region, and Ward's triangle was measured using dual-energy X-ray absorptiometry (DXA) in 118 women with osteoporotic vertebral collapse (average age 65 years), divided into four groups according to numbers and SD of vertebral deformation below norms: group 1:-3SD deformations only; group 2: one-4SD deformation; group 3: two-four-4SD deformations; and group 4: 5 or more-4SD deformations. There were no significant differences between the groups. Results were compared with those from 80 premenopausal (average age 32 years, range 20–40 years) and 109 postmenopausal normal women (average age 64, range 60–70 years). Mean BMD in osteoporotic group 1 was lower than premenopausal normal women by 32% at the lumbar spine, 31% femoral neck, 30% trochanteric region, and 44% at Ward's triangle, and postmenopausal controls by 17% lumbar spine, 16% femoral neck, 17% trochanter, and 14% Ward's triangle. There was a clear trend to reduction in mean BMD between osteoporotic groups 1 and 4 at all four measured sites with significant differences at the spine of 0.102 g/cm2 (P<0.01) and Ward's triangle 0.059 g/cm2 (P<0.01). When compared with premenopausal controls, there was a reduction in mean BMD between osteoporotic groups 1 and 4 of 10% at the lumbar spine, 7% femoral neck, 8% trochanteric region, and 13% Ward's triangle. Receiver operating characteristic analysis showed no significant differences in diagnostic sensitivities among the four measured sites for vertebral fractures. We conclude from this crosssectional data that the majority of bone loss in spinal osteoporosis occurs before the onset of fractures.

The assessment of skeletal integrity by the measurement of ultrasonic velocity through the calcaneus has only recently become widely available and is usually made in conjunction with the measurement of broadband ultrasonic attenuation. Using data obtained with a contact ultrasonic bone analyser (CUBA) system, this report examines whether ultrasonic studies of the heel require the measurement of true velocity of sound in the calcaneus (Vbone), or whether heel velocity (Vheel, defined as the mean velocity through bone and soft tissue) or time of flight velocity (Vtof, defined as the mean velocity between the two transducers) are adequate surrogates. The populations selected for study were 15 healthy young women (group 1, mean age 26 years), 231 healthy peri- and postmenopausal women (group 2, mean age 52 years) and 33 osteoporotic women with confirmed vertebral fracture (group 3, mean age 66 years). Precision was studied by performing 10 repeated scans on the subjects in group 1 and duplicate scans on 144 women randomly selected in groups 2 and 3. Precision was expressed as the percentage coefficient of variation (CV). Both precision studies yielded similar results. The precisions (and 5% to 95% ranges) for all groups combined were: Vbone 2.71% (1465–1809 m/s); Vheel, 1.10% (1511–1646 m/s); Vtof, 0.70% (1349–1425 m/s). Although the precision data suggest Vtof should be preferred, when the range of clinical values is taken into account the smaller CV is exactly cancelled by the narrower range. To demonstrate this numerically it is proposed to introduce a new measure of precision, the standardized coefficient of variation (SCV), defined as the percentage CV divided by the percentage ratio of the range over the mean. SCV had a value of 12.7% for Vtof and 12.8% for Vbone and Vheel. For comparison a SCV of 2.2% was estimated for dual X-ray absorptiometry (DXA). Thus the measurement of ultrasonic velocity through the calcaneus compares equally in terms of CV, but not in terms of SCV. A scatter plot of Vbone against Vtof gave a significantly poorer correlation (r=0.828) than that of Vbone against Vheel (r=0.984). This latter correlation can be explained by theoretical studies demonstrating convergence of the two measurements when the velocity through the bone equals that through soft tissue (1540 m/s). Since the measurement of Vheel dispenses with the need to determine soft tissue thickness over the calcaneus, it is the optimum velocity parameter for the CUBA system.

We report a study of broadband ultrasonic attenuation (BUA) in the calcaneus in 248 women. Measurements were performed with a Walker-Sonix UBA-575 ultrasonic bone analyser. The populations studied were 15 healthy young volunteers (group 1, mean age 26 years), 200 healthy pre- and postmenopausal women (group 2, mean age 53 years) and 33 osteoporotic women with vertebral crush fractures (group 3, mean age 66 years). Subjects in group 1 each had 10 repeated measurements of their right heel. Duplicate BUA measurements in the right heel were performed in 96 subjects and bilateral scans in a further 87 women in group 2. The remaining 17 subjects in group 2 and those in group 3 had a single scan of the right heel. All women in groups 2 and 3 had dual X-ray absorptiometry (DXA) scans of the lumbar spine and femoral neck.

We have reviewed our experience over the past 5 years of 32 thyroid scans in Hashimoto's thyroiditis. A wide variety of images were obtained, the most common finding being that of an enlarged gland with diffusely increased tracer uptake, a pattern identical to that found in Graves' disease (eight patients). Of the remainder, four scans were normal, four showed an enlarged gland with normal tracer uptake, five a multinodular gland with normal tracer uptake, five a multinodular gland with high tracer uptake, five a single non-functioning nodule and in one patient there was low tracer uptake by the gland. It is apparent that the thyroid scan in Hashimoto's thyroiditis can mimic a wide range of thyroid disorders. Thus, taken in isolation, the scan findings can be misleading and should be evaluated in conjunction with current biochemistry.

Clinical studies with progestagens indicate an antiresorptive effect on bone and suggest they stimulate bone formation. Protection against bone loss is weaker than that with oestrogen. The more oestrogen-like progestagens may have a greater protective effect. In menstruating women progestagens cause ovarian suppression which outweighs any potential benefit with respect to bone.For postmenopausal women who do not wish to experience cyclical bleeding, tibolone seems appropriate for prevention of osteoporosis.

A group of 26 patients aged 47–81 years (average 67) with spinal osteoporosis and back pain for more than 6 months were investigated with planar and SPECT bone scintigraphy and anterior and lateral x‐rays of the thoracolumbar spine. Abnormal activity on bone scintigraphy was found in all patients, of whom 22 had multiple lesions. A total of 17 (65%) patients had abnormal activity associated with collapsed vertebral bodies, 5 (19%) had degenerative disk disease, and 21 (81%) had facetal joint disease. Of 112 lesions identified by SPECT, 60 (54%) were localized to the apophyseal joints. Facetal lesions were commoner in those patients with more collapsed vertebrae, and 32 facetal lesions (54%) were associated with collapse of the vertebra immediately above or below. Bone scintigraphy findings suggest that in some individuals with osteoporosis and chronic back pain, collapse of the vertebral body or degenerative disk disease are causes of pain. However, the high frequency of increased apophyseal joint activity suggests that the facet joints may also be an important site of origin of pain in these individuals. Bone scintigraphy may identify a subgroup of osteoporotic patients with chronic back pain who would benefit from treatment to the facet joints.

Bone single photon emission tomography (SPET) of the knees has been shown to be of diagnostic value for the investigation of knee pain. This study compared bone SPET with magnetic resonance imaging (MRI) for the diagnosis of knee disorders. Thirty-six patients were studied with both modalities, performed an average of 4 months apart (range 0–10 months). There was agreement on the presence or absence and nature of pathology in 24 (67) patients. In a further three patients, there was an abnormal SPET with equivocal change for the same pathology on MRI. Equivocal changes on both modalities for the same pathology were found in one patient. Three patients had abnormalities on MRI with normal SPET, with the remaining patients having equivocal or non-specific changes on one modality only. In the majority of patients, there was agreement on the presence or absence of pathology and the nature of pathology with both modalities. Significant pathology detected on MRI was also identified by bone SPET. This initial study suggests that further work should be undertaken to evaluate the role of bone SPET as a screening test for the evaluation of knee disorders and its role in relation to MRI is justified.

Serum sex hormone binding globulin, thyroxine binding globulin, cortisol binding globulin and vitamin D binding globulin, together with total levels of the appropriate bound hormones, were determined in 21 epileptic subjects who had been stabilised by long-term anticonvulsant therapy.Serum sex hormone binding globulin capacity was higher in these patients than in appropriate control groups (men p<0.05; women p<0.01), and values correlated with serum phenytoin levels in the female subjects (p<0.01). Thyroxine binding globulin levels were unaffected by anticonvulsants, but significant reductions in serum thyroxine (men p<0.05; women p<0.001) and triiodothyronine (men p<0.05; women p<0.01) were observed. Cortisol binding globulin capacity was appreciably elevated in patients of either sex (p<0.001), and in the women this was accompanied by a reduction in serum cortisol (p<0.001) and a significant correlation with the serum phenytoin concentration (p<0.01). Neither vitamin D binding globulin capacity nor serum 25-hydroxycholecalciferol levels were influenced by anticonvulsants in this study.It is concluded that anticonvulsant drug therapy causes widespread alterations in the normal homeostasis between hormones and their serum binding globulins. Such alterations may well have clinical significance.

Computed tomography has been employed for the localisation of parathyroid tissue in 26 patients with primary hyperparathyroidism. In 14 of these selective venous catheter studies with parathyroid hormone assay were also undertaken. Computed tomography proved unreliable, identifying only 39 per cent whereas the cervical venous hormone assay studies localised 69 per cent of lesions correctly—a figure which is in agreement with several other groups. On balance our results suggest that neither technique should be routinely employed pre-operatively but that, following unsuccessful parathyroid surgery, the most useful localisation technique remains venous hormone assay.

Reliable pre-operative localisation of parathyroid tumours can be of value in surgery for primary hyperparathyroidism, and particularly so where re-exploration of the neck is required. Neck vein catheterisation and parathyroid hormone radioimmunoassay have been suggested as a sensitive means of tumour localisation, and we report our experience of the technique over the last five years.A total of 46 patients with primary hyperparathyroidism had 50 studies performed with positive localisation and a pre-operative prediction made on 38 occasions (76%). Forty-two operations were carried out and a parathyroid tumour confirmed in 39 cases for a localisation efficiency of 69 per cent. No negative neck exploration followed a positive localisation. Twelve studies were performed in patients with renal osteodystrophy and localisation to a single site was achieved on only three occasions.It is concluded that neck vein catheterisation and parathyroid hormone assay can correctly localise parathyroid tumours in most cases of primary hyperparathyroidism, but is is suggested that its use be restricted to selected cases such as those subjects with previous negative neck exploration or patients for whom prolonged or repeated surgery may be a particular hazard.

Twenty adult epileptic out-patients who had received anticonvulsant therapy for a mean duration of 15 years were assessed for clinical, biochemical, radioisotopic and bone biopsy evidence of osteomalacia. Occasional biochemical abnormalities were demonstrated but no individual subject was found to have osteomalacia. There is increasing evidence to cast doubt on the existence of a strong relationship between anticonvulsant drugs and osteomalacia. This evidence is reviewed and it is concluded that in the presence of adequate sunlight exposure anticonvulsant therapy alone is most unlikely to lead to osteomalacia in adults.

Clinical experience with cyclical etidronate for the treatment of osteoporosis was reviewed in 69 consecutive patients. Six patients stopped treatment either due to adverse effects (5) or the decision to take hormone replacement therapy (HRT) (1). Bone mineral density (BMD) measurements using dual energy X-ray absorptiometry (DXA) were obtained in 63 patients (33 with spinal osteoporotic fractures and 30 with osteopenia) before and 1 year after treatment. BMD increased by an average of 4.50% (p<0.001) in the lumbar spine (range +14% to −12%) and 5.5% (p<0.01) at Ward's triangle (range +31% to −13%) while there was no significant change at the femoral neck (range +11% to −12%) and greater trochanter (range +12% to −15%). Significant rises in BMD were found at the lumbar spine and Ward's triangle in both osteoporotic and osteopenic groups. Of patients analysed after 1 year, 83% had an increased bone mass at the lumbar spine and 55% at the femoral neck.

Summary The bone scan may be of value in the assessment of patients with metabolic bone disease. However the superiority of the bone scan when compared to radiology in conditions such as renal osteodystrophy, osteomalacia, primary hyperparathyroidism, and osteoporosis requires substantiation with the newer radiopharmaceuticals which have a higher affinity for bone. Two methods of quantitating skeletal uptake of tracer have been assessed to try to remove the subjective aspect of bone scan evaluation. Measurements of bone to soft tissue ratios have proved clinically disappointing, but 24 hour whole body retention of diphosphonate appears to provide a sensitive index of increased bone turnover.

Patients with a wide variety of rheumatological conditions can be usefully investigated by nuclear medicine techniques and particularly by bone scintigraphy. This aspect of nuclear medicine work is increasing and the trend can be expected to continue. The principal conditions that can be imaged are sports medicine injuries, osteomyelitis, avascular necrosis, reflex sympathetic dystrophy syndrome, enthesopathies and biomechanical stress lesions, inflammatory arthropathies, metabolic bone disease and miscellaneous bone conditions such as costo-chondritis. Single photon emission tomography (SPECT) has provided new indications for bone scintigraphy such as the evaluation of spondylolysis and facet syndrome in the spine and of meniscal tears and ligamental lesions in the knee.