Differential effects of teriparatide on regional bone formation using 18F‐fluoride positron emission tomography

Teriparatide increases skeletal mass, bone turnover markers, and bone strength, but local effects on bone tissue may vary between skeletal sites. We used positron emission tomography (PET) to study ¹⁸F‐fluoride plasma clearance (K_i) at the spine and standardized uptake values (SUVs) at the spine, pelvis, total hip, and femoral shaft in 18 postmenopausal women with osteoporosis. Subjects underwent a 1‐hour dynamic scan of the lumbar spine and a 10‐minute static scan of the pelvis and femurs at baseline and after 6 months of treatment with 20 µg/day teriparatide. Blood samples were taken to derive the arterial input function and lumbar spine K_i values evaluated using a three‐compartment model. SUVs were calculated for the spine, pelvis, total hip, and femoral shaft. After 6 months treatment with teriparatide, spine K_i values increased by 24% (p = .0003), while other model parameters were unchanged except for the fraction of tracer going to bone mineral (k₃/[k₂ + k₃]), which increased by 23% (p = .0006). In contrast to K_i, spine SUVs increased by only 3% (p = .84). The discrepancy between changes in K_i and SUVs was explained by a 20% decrease in ¹⁸F^? plasma concentration. SUVs increased by 37% at the femoral shaft (p = .0019), 20% at the total hip (p = .032), and 11% at the pelvis (p = .070). Changes in bone turnover markers and BMD were consistent with previous trials. We conclude that the changes in bone formation rate during teriparatide treatment as measured by ¹⁸F^? PET differ at different skeletal sites, with larger increases in cortical bone than at trabecular sites. © 2011 American Society for Bone and Mineral Research.     

Correlation between mechanical stress by finite element analysis and 18F‐fluoride PET uptake in hip osteoarthritis patients

¹⁸F‐fluoride positron emission tomography (¹⁸F‐fluoride PET) is a functional imaging modality used primarily to detect increased bone metabolism. Increased ¹⁸F‐fluoride PET uptake suggests an association between increased bone metabolism and load stress at the subchondral level. This study therefore examined the relationship between equivalent stress distribution calculated by finite element analysis and ¹⁸F‐fluoride PET uptake in patients with hip osteoarthritis. The study examined 34 hips of 17 patients who presented to our clinic with hip pain, and were diagnosed with osteoarthritis or pre‐osteoarthritis. The hips with trauma, infection, or bone metastasis of cancer were excluded. Three‐dimensional models of each hip were created from computed tomography data to calculate the maximum equivalent stress by finite element analysis, which was compared with the maximum standardized uptake value (SUV_max) examined by ¹⁸F‐fluoride PET. The SUV_max and equivalent stress were correlated (Spearman's rank correlation coefficient ρ = 0.752), and higher equivalent stress values were noted in higher SUV_max patients. The correlation between SUV_max and maximum equivalent stress in osteoarthritic hips suggests the possibility that ¹⁸F‐fluoride PET detect increased bone metabolism at sites of stress concentration. This study demonstrates the correlation between mechanical stress and bone remodeling acceleration in hip osteoarthritis. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:78–83, 2015.     

Detection of incidental colorectal tumours with 18F‐labelled 2‐fluoro‐2‐deoxyglucose positron emission tomography/computed tomography scans: results of a prospective study

Aim This study assessed the clinical significance of incidental colorectal 2‐fluoro‐2‐deoxyglucose (FDG) uptake using ¹⁸F‐FDG positron emission tomography/computed tomography (PET/CT) scans and evaluated the importance of colonoscopy when incidental colorectal FDG uptake was observed. Method A prospective study was designed and conducted at a single institution over a 2‐year period. In patients undergoing PET/CT scans, all with FDG uptake in the colorectum were assigned to have colonoscopy and biopsy. The value of PET/CT scanning was studied by comparison with the colonoscopy and biopsy results. Results Among 10 978 PET/CT scans, one or more focal uptakes of FDG in the colorectum were observed in 148 (1.35%) patients. In 136 valid patients, malignant colorectal tumours and polyps were found in 23.5% and 20.5%, respectively,, while the colon in the other 56% was normal. A higher false‐positive rate was found in the right colon compared with the distal colorectum (66.2%vs 36.7%, P = 0.004). A significant increase of the maximum standardized uptake (SUVmax) value was found among normal, polyps and cancer groups. Multivariate analysis revealed that SUVmax was the risk factor for predicting colorectal cancer or polyps and FDG uptake in the right colon was a negative predictive factor for finding cancers or polyps. Conclusions Our study proves the necessity of colonoscopy when incidental FDG uptake is found on PET/CT imaging. The false‐positive FDG uptake is more commonly observed in the right colon. Although the SUVmax value is higher in cancer patients, a high SUVmax value does not necessarily result in malignancies.     

A longitudinal HR‐pQCT study of alendronate treatment in postmenopausal women with low bone density: Relations among density,cortical and trabecular microarchitecture,biomechanics, and bone turnover

The goal of this study was to characterize longitudinal changes in bone microarchitecture and function in women treated with an established antifracture therapeutic. In this double‐blind, placebo‐controlled pilot study, 53 early postmenopausal women with low bone density (age = 56 ± 4 years; femoral neck T‐score = ?1.5 ± 0.6) were monitored by high‐resolution peripheral quantitative computed tomography (HR‐pQCT) for 24 months following randomization to alendronate (ALN) or placebo (PBO) treatment groups. Subjects underwent annual HR‐pQCT imaging of the distal radius and tibia, dual‐energy X‐ray absorptiometry (DXA), and determination of biochemical markers of bone turnover (BSAP and uNTx). In addition to bone density and microarchitecture assessment, regional analysis, cortical porosity quantification, and micro‐finite‐element analysis were performed. After 24 months of treatment, at the distal tibia but not the radius, HR‐pQCT measures showed significant improvements over baseline in the ALN group, particularly densitometric measures in the cortical and trabecular compartments and endocortical geometry (cortical thickness and area, medullary area) (p < .05). Cortical volumetric bone mineral density (vBMD) in the tibia alone showed a significant difference between treatment groups after 24 months (p < .05); however, regionally, significant differences in Tb.vBMD, Tb.N, and Ct.Th were found for the lateral quadrant of the radius (p < .05). Spearman correlation analysis revealed that the biomechanical response to ALN in the radius and tibia was specifically associated with changes in trabecular microarchitecture (|ρ| = 0.51 to 0.80, p < .05), whereas PBO progression of bone loss was associated with a broad range of changes in density, geometry, and microarchitecture (|ρ| = 0.56 to 0.89, p < .05). Baseline cortical geometry and porosity measures best predicted ALN‐induced change in biomechanics at both sites (ρ > 0.48, p < .05). These findings suggest a more pronounced response to ALN in the tibia than in the radius, driven by trabecular and endocortical changes. © 2010 American Society for Bone and Mineral Research.     

The effect of adding PTH(1–84) to conventional treatment of hypoparathyroidism: A randomized,placebo‐controlled study

In hypoparathyroidism, plasma parathyroid hormone (PTH) levels are inadequate to maintain plasma calcium concentration within the reference range. On conventional treatment with calcium supplements and active vitamin D analogues, bone turnover is abnormally low, and BMD is markedly increased. We aimed to study the effects of PTH‐replacement therapy (PTH‐RT) on calcium‐phosphate homeostasis and BMD. In a double‐blind design, we randomized 62 patients with hypoparathyroidism to daily treatment with PTH(1–84) 100 µg or similar placebo for 24 weeks as add‐on therapy to conventional treatment. Compared with placebo, patients on PTH(1–84) reduced their daily dose of calcium and active vitamin D significantly by 75% and 73%, respectively, without developing hypocalcemia. However, hypercalcemia occurred frequently during the downtitration of calcium and active vitamin D. Plasma phosphate and renal calcium and phosphate excretion did not change. Compared with placebo, PTH(1–84) treatment significantly increased plasma levels of bone‐specific alkaline phosphatase (+226% ± 36%), osteocalcin (+807% ± 186%), N‐terminal propeptide of procollagen 1 (P1NP; +1315% ± 330%), cross‐linked C‐telopeptide of type 1 collagen (CTX; +1209% ± 459%), and urinary cross‐linked N‐telopeptide of type 1 collagen (NTX; (+830% ± 165%), whereas BMD decreased at the hip (?1.59% ± 0.57%), lumbar spine (?1.76% ± 1.03%), and whole body (?1.26% ± 0.49%) but not at the forearm. In conclusion, the need for calcium and active vitamin D is reduced significantly during PTH‐RT, whereas plasma calcium and phosphate levels are maintained within the physiologic range. In contrast to the effect of PTH(1–84) treatment in patients with osteoporosis, PTH‐RT in hypoparathyroidism causes a decrease in BMD. This is most likely due to the marked increased bone turnover. Accordingly, PTH‐RT counteracts the state of overmineralized bone and, during long‐term treatment, may cause a more physiologic bone metabolism. © 2011 American Society for Bone and Mineral Research