Hyperprolactinemia Due to Prolactinoma has an Adverse Impact on Bone Health with Predominant Impact on Trabecular Bone: A Systematic Review and Meta-Analysis.

BACKGROUND: No meta-analysis has holistically analysed and summarized the effect of prolactin excess due to prolactinomas on bone mineral metabolism. We undertook this meta-analysis to address this knowledge-gap. METHODS: Electronic databases were searched for studies having patients with hyperprolactinemia due to prolactinoma and the other being a matched control group. The primary outcome was to evaluate the differences in BMD Z-scores at different sites. The secondary outcomes of this study were to evaluate the alterations in bone mineral density, bone mineral content and the occurrence of fragility fractures. RESULTS: Data from 4 studies involving 437 individuals was analysed to find out the impact of prolactinoma on bone mineral metabolism. Individuals with prolactinoma had significantly lower Z scores at the lumbar spine [MD -1.08 (95 % CI: -1.57 - -0.59); P < 0.0001; I2 = 54 % (moderate heterogeneity)] but not at the femur neck [MD -1.31 (95 % CI: -3.07 - 0.45); P = 0.15; I2 = 98 % (high heterogeneity)] as compared to controls. Trabecular thickness of the radius [MD -0.01 (95 % CI: -0.02 - -0.00); P = 0.0006], tibia [MD -0.01 (95 % CI: -0.02 - -0.00); P=0.03] and cortical thickness of the radius [MD -0.01 (95 % CI: -0.19 - -0.00); P = 0.04] was significantly lower in patients with prolactinoma as compared to controls. The occurrence of fractures was significantly higher in patients with prolactinoma as compared to controls [OR 3.21 (95 % CI: 1.64 - 6.26); P = 0.0006] Conclusion: Bone mass is adversely affected in patients with hyperprolactinemia due to prolactinoma with predominant effects on the trabecular bone.

Dual-Energy CT-based Opportunistic Volumetric Bone Mineral Density Assessment of the Distal Radius.

Background In patients with distal radius fractures (DRFs), low bone mineral density (BMD) is associated with bone substitute use during surgery and bone nonunion, but BMD information is not regularly available. Purpose To evaluate the feasibility of dual-energy CT (DECT)-based BMD assessment from routine examinations in the distal radius and the relationship between the obtained BMD values, the occurrence of DRFs, bone nonunion, and use of surgical bone substitute. Materials and Methods Scans in patients who underwent routine dual-source DECT in the distal radius between January 2016 and December 2021 were retrospectively acquired. Phantomless BMD assessment was performed using the delineated trabecular bone of a nonfractured segment of the distal radius and both DECT image series. CT images and health records were examined to determine fracture severity, surgical management, and the occurrence of bone nonunion. Associations of BMD with the occurrence of DRFs, bone nonunion, and bone substitute use at surgical treatment were examined with generalized additive models and receiver operating characteristic analysis. Results This study included 263 patients (median age, 52 years; IQR, 36-64 years; 132 female patients), of whom 192 were diagnosed with fractures. Mean volumetric BMD was lower in patients who sustained a DRF (93.9 mg/cm3 vs 135.4 mg/cm3; P < .001), required bone substitutes (79.6 mg/cm3 vs 95.5 mg/cm3; P < .001), and developed bone nonunion (71.1 mg/cm3 vs 96.5 mg/cm3; P < .001). Receiver operating characteristic curve analysis identified these patients with an area under the curve of 0.71-0.91 (P < .001). Lower BMD increased the risk to sustain DRFs, develop bone nonunion, and receive bone substitutes at surgery (P < .001). Conclusion DECT-based BMD assessment at routine examinations is feasible and could help predict surgical bone substitute use and the occurrence of bone nonunion in patients with DRFs. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Carrino in this issue.

Effect of gold nanoparticles distribution radius on photothermal therapy efficacy.

Lasers are used in various fields, however, in the medical field, they are mainly used for incision or chemotherapy. Photothermal therapy (PTT) is an anti-cancer treatment technique that uses lasers and the photothermal effect to increase the temperature of tumor tissue and induce its death. In this study, the therapeutic effect of PTT using gold nanoparticles as a photothermal converter was analyzed numerically for the occurrence of squamous cell carcinoma inside a skin section consisting four layers. Numerical modeling was implemented to calculate the temperature distribution inside the biological tissue while varying the distribution radius of gold nanoparticles in the tumor tissue, the number of injections, and the intensity of the irradiating laser. For the given situation, the optimal treatment effect was observed when the distribution radius ratio of the injected gold nanoparticles (GNPs) was 1, the number of injections was 7, and the intensity of the irradiated laser was 52 mW. Three apoptotic variables were used to quantitively evaluate the effect of PTT in each case and thus suggest the optimal treatment effect. However, although the temperature range at which apoptosis occurs is known, the maintenance of that temperature range is still under research and the temporal influence of apoptosis remains to be determined.

Risk of radial head arthroplasty revision is correlated with radial head diameter: a multicenter analysis of 405 cases.

BACKGROUND: Radial head arthroplasty (RHA) is commonly used for the treatment of comminuted radial head fractures. Indications as well as implant types continue to evolve. RHA has had good outcomes with midterm longevity. The literature is limited to small case series with varying implant types, and larger studies are needed to determine the optimal implant type and radial head diameter. METHODS: A retrospective analysis of RHA cases performed by 75 surgeons at 14 medical centers in an integrated health care system between 2006 and 2017 was completed. Patient demographics, comorbidities, implant type and head diameter, and indications for revision were recorded. Patients' in-person clinical visit data were recorded. Patients were also contacted via telephone at a minimum of 2 years to obtain abbreviated Disabilities of the Arm, Shoulder, and Hand questionnaire and Oxford scores. Implant survivorship was also captured within our integrated system. RESULTS: 405 cases met our inclusion criteria. Mean age was 51.5 ± 15.5 years (range 16-88 years) and more common in females (62%). Chart review and telephone follow-up was performed at a mean of 68.9 ± 31.5 months (range 24-146 months). Our study found that revision rate was positively correlated with increasing radial head diameter. A 26-mm head had 7.7 odds of revision compared to a size 18-mm head (95% confidence interval 1.2-150.1). More than 95% of revision cases were performed within the first 36 months of the index procedure. Obese patients had a significantly lower mean postoperative Oxford score (35.5) compared to controls (38.3) (P = .02). There was a significantly higher overall reoperation rate for terrible triad (18.4%) vs. isolated injuries (10.4%) (P = .04). There was no difference between Acumed Anatomic and Evolve radial head implants in overall reoperation, implant revision, postoperative range of motion, or patient-reported outcomes. CONCLUSIONS: Risk of revision is directly correlated with implanted radial head diameter. There were no differences in outcomes and complications between the 2 main implants used. Individuals who did not undergo a revision by 3 years' time tend to retain the implant. Terrible triad injuries had a higher all-cause reoperation rate than isolated radial head fractures, but no difference in the rate of RHA revision. These data reinforce the practice of downsizing radial head implant diameter.

Bone characteristics of autosomal dominant hypophosphatemic rickets patients.

OBJECTIVE: Autosomal dominant hypophosphatemic rickets (ADHR) is a rare disease caused by activating mutations in fibroblast growth factor 23 (FGF23) gene. With FGF23 activation, ADHR is a good model to explore the effects of FGF23 on skeletal development and mineralization. However, the bone microarchitecture of ADHR patients is poorly investigated. This study aims to illustrate the bone properties of ADHR patients and clarify the effect of FGF23 on load bearing and non-load bearing bone. METHODS: Bone microarchitectures of 11 ADHR subjects and sex- and age-matched healthy controls were analyzed by HR-pQCT. The effect of FGF23 mutations on load bearing and non-load bearing bone was explored by comparison of bone microarchitecture in distal radius and distal tibia. The BMD, bone microarchitecture and bone strength were compared between 7 ADHR patients and 7 age- and sex-matched XLH patients. RESULTS: Among 11 subjects with FGF23 mutations, 10 patients presented with obvious symptoms, five of which had received 1-3 years of iron supplement, neutral phosphate, and calcitriol treatments. The symptomatic patients presented with low bone density and fractures in X rays, with decreased Z score of aBMD (L1-L4: -1.3 ± 1.4, femoral neck: -2.1 ± 1.8, total hip: -1.85 ± 1.6). Compared with controls, HR-pQCT analysis of 5 untreated ADHR patients showed increased total area (+61.6 %, p = 0.03) and cortical perimeter (+17.2 %, p = 0.03) in distal radius. No significant differences were found in other parameters in distal radius. In distal tibia, the patients presented obvious defects in cancellous bone, with decreased trabecular vBMD (-62.9 %, p = 0.003), trabecular BV/TV (-48.7 %, p = 0.003) and trabecular number (-42.2 %, p = 0.001). The trabecular separation (+113.3 %, p = 0.007) and trabecular network inhomogeneity (+226.7 %, p = 0.001) were accordingly increased. In addition to another 5 treated patients, the bone microarchitecture changes revealed similar pattern, but the increase of total area and cortical perimeter in distal radius was no longer statistically significant. The non-symptomatic ADHR patient demonstrated slightly decreased total vBMD, trabecular vBMD and trabecular BV/TV in distal tibia. The changing pattern of bone geometry and microarchitecture of ADHR patients were similar to XLH patients but showed less deficit and stronger bone strength. CONCLUSION: ADHR patients presented increased total area and cortical perimeter in distal radius, and obvious defect in cancellous bone in distal tibia. FGF23 have impairment effect on trabecular bone especially in weight bearing site.

Circumferential periosteal block versus hematoma block for the reduction of distal radius and ulna fractures: a randomized controlled trial.

PURPOSE: To assess the analgesic efficacy of the circumferential periosteal block (CPB) and compare it with the conventional fracture hematoma block (HB). METHODS: This study was a prospective single-center randomized controlled trial performed in a national orthopedic hospital. Fifty patients with displaced distal radius (with or without concomitant ulna) fractures requiring reduction were randomized to receive either CPB or HB prior to the reduction. Pain was sequentially measured using the visual analogue scale (VAS) across three stages; before administration of local anesthesia (baseline), during administration (injection) and during manipulation and immobilization (manipulation). Further, the effect of demographic factors on the severity of pain was analyzed in multivariate regression. Finally, complications and end outcomes were compared across both techniques. RESULTS: Patients receiving CPB experienced significantly less pain scores during manipulation (VAS = 0.64) compared with HB (VAS = 2.44) (p = < 0.0001). There were no significant differences between groups at baseline (P = 0.55) and injection (P = 0.40) stages. CONCLUSION: The CPB provides a superior analgesic effect over the conventional HB with no documented complications in either technique. LEVEL OF EVIDENCE: Therapeutic Level II.

A Comparison of Arc of Motion, Radiological Parameters of the Wrist and Patient Rated Wrist Evaluation between Adult Transfusion Dependent Thalassemics and Normal Subjects.

Background: Bony deformities and arthropathies have been noticed in thalassemia patients. The aim of this study is to compare the arc of motion and radiological parameters of the wrist and patient rated wrist evaluation (PRWE) between adult transfusion-dependent thalassemics and normal subjects. Methods: An observational cross-sectional study was done in the department of orthopaedics over a period of 2 years where a total of 30 skeletally mature thalassemia major patients (group A) were assessed. The data was then compared with the data of demographically matched 30 healthy adults (group B). Arc of motion of the dominant wrist that included flexion, extension, radial and ulnar deviation, pronation and supination was measured using a handheld goniometer for both groups. Radiographs of the dominant wrist were obtained in both groups and used to determine the radial height, radial articular angle and carpal slip. PRWE was used to assess the function of the wrist. A p-value of <0.05 was considered statistically significant. Results: Clinical abnormalities at the wrist joint were found in 80% of thalassaemia patients. There was a statistically significant increase in ulnar deviation, wrist extension and decrease in wrist flexion in group A compared to group B. Radiological abnormalities were found in 100% of thalassaemia patients. All the radiological parameters were significantly increased in group A compared to group B. There were no differences in PRWE scores between both groups. Conclusion: Clinical and radiological changes of wrist joint occur in skeletally mature thalassaemia major patients due to shortened ulna compared to healthy adults. This may be due to disease itself, bone marrow expansion, osteopenia, drug (chelating agent) or iron toxicity. Understanding the changes at the wrist in patients with thalassemia major is important to increasing the life expectancy of these patients. Level of Evidence: Level IV (Diagnostic).

Association of Vitamin D and Parathyroid Hormone Status With the Aging-Related Decline of Bone Microarchitecture in Older Men: The Prospective Structure of Aging Men's Bones (STRAMBO) Study.

Poor vitamin D status and high parathyroid hormone (PTH) level are associated with impaired bone microarchitecture, but these data are mainly cross-sectional. We studied the association of the baseline PTH and 25-hydroxycholecalciferol (25OHD) levels with the prospectively assessed deterioration of bone microarchitecture and in estimated bone strength in older men. Distal radius and tibia bone microarchitecture was assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT) at baseline, then after 4 and 8 years in 826 men aged 60-87 years. At distal radius, total bone mineral density (Tt.BMD), cortical thickness (Ct.Thd ), cortical area (Ct.Ar), cortical BMD (Ct.BMD), and trabecular BMD (Tb.BMD) decreased, whereas trabecular area (Tb.Ar) increased more rapidly in men with 25OHD ≤20 ng/mL versus the reference group (>30 ng/mL). Men with 25OHD ≤10 ng/mL had faster decrease in reaction force and failure load than men with 25OHD >30 ng/mL. At the distal tibia, Tt.BMD, Ct.Thd , Ct.Ar, Ct.BMD, failure load, and reaction force decreased, whereas Tb.Ar increased more rapidly in men with 25OHD between 10 and 20 ng/mL versus the reference group. The results were similar when 12 ng/mL was used as a threshold of severe vitamin D deficiency. At distal radius, men with PTH levels above the median (>44 pg/mL) had more rapid decrease in Tt.BMD, Ct.Ar, Ct.BMD, Ct.Thd , reaction force, and failure load, and more rapid increase in Tb.Ar versus the lowest quartile (≤34 pg/mL). At the distal tibia, men in the highest PTH quartile had faster decrease in Tt.BMD, Ct.Thd , Ct.Ar, Ct.BMD, reaction force, and failure load and faster increase in Tb.Ar versus the lowest quartile. The results were similar in men with glomerular filtration rate >60 mL/min. The results were similar in men who took no vitamin D or calcium supplements for 8 years. In summary, vitamin D deficiency and secondary hyperparathyroidism are associated with more rapid prospectively assessed cortical and trabecular bone decline in older men. © 2022 American Society for Bone and Mineral Research (ASBMR).

Randomized controlled trial of daily teriparatide, weekly high-dose teriparatide, or bisphosphonate in patients with postmenopausal osteoporosis: The TERABIT study.

PURPOSE: The effects of daily teriparatide (20 µg) (D-PTH), weekly high-dose teriparatide (56.5 µg) (W-PTH), or bisphosphonates (BPs) on areal bone mineral density (aBMD), bone turnover markers (BTMs), volumetric BMD (vBMD), microarchitecture, and estimated strength were investigated in postmenopausal osteoporosis patients. METHODS: The study participants were 131 women with a history of fragility fractures. They were randomized to receive D-PTH, W-PTH, or BPs (alendronate or risedronate) for 18 months. Dual-energy X-ray absorptiometry (DXA), BTMs, and high-resolution peripheral quantitative CT (HR-pQCT) parameters were evaluated at baseline and after 6 and 18 months of treatment. The primary endpoint was the change (%) in cortical thickness (Ct.Th) after 18 months' treatment compared with baseline. RESULTS: DXA showed that D-PTH, W-PTH, and BPs increased lumbar spine aBMD (+12.0%, +8.5%, and +6.8%) and total hip aBMD (+3.0%, +2.1%, and +3.0%), but D-PTH and W-PTH decreased 1/3 radius aBMD (-4.1%, -3.0%, -1.4%) after 18 months. On HR-pQCT, D-PTH increased trabecular vBMD (Tb.vBMD) at the distal radius and tibia after 18 months (+6.4%, +3.7%) compared with the BPs group, decreased cortical volumetric tissue mineral density (Ct.vTMD) (-1.8%, -0.9%) compared with the other groups, increased Ct.Th (+1.3%, +3.9%), and increased failure load (FL) (+4.7%, +4.4%). W-PTH increased Tb.vBMD (+5.3%, +1.9%), maintained Ct.vTMD (-0.7%, +0.2%) compared with D-PTH, increased Ct.Th (+0.6%, +3.6%), and increased FL (+4.9%, +4.5%). The BPs increased Tb.vBMD only in the radius (+2.0%, +0.2%), maintained Ct.vTMD (-0.6%, +0.3%), increased Ct.Th (+0.5%, +3.4%), and increased FL (+3.9%, +2.8%). CONCLUSIONS: D-PTH and W-PTH comparably increased Ct.Th, the primary endpoint. D-PTH had a strong effect on trabecular bone. Although D-PTH decreased Ct.vTMD, it increased Ct.Th and total bone strength. W-PTH had a moderate effect on trabecular bone, maintained Ct.vTMD, and increased Ct.Th and total bone strength to the same extent as D-PTH.

Cessation of ambulation results in a dramatic loss of trabecular bone density in boys with Duchenne muscular dystrophy (DMD).

Glucocorticoids are currently used to improve muscle strength and prolong ambulation in boys with DMD although the effect on bone health is still unclear. The aim of this study was to compare bone strength in healthy children and boys with DMD and investigate the interaction between diminished muscle function, loss of ambulation and high dose oral steroids, over a two year time frame. Fifty children were studied, 14 healthy boys (HB), 13 boys with DMD who remained ambulant (DMD-RA) and 23 boys with DMD who lost ambulation (DMD-LA). All boys with DMD had taken oral glucocorticoids. Peripheral quantitative computed tomography was used to measure bone geometry, density, strength and muscle mass of the non-dominant tibia and radius. Measurements were made at baseline, 12 and 24 months at the distal metaphysis and mid diaphysis sites. Differences between the three groups were evaluated using ANOVA and a repeated measures model. There were no significant differences in age between the groups: mean age was 9.4, 8.7 and 8.8 years for HB, DMD-RA and DMD-LA, respectively. There was no significant difference in steroid exposure between the DMD groups. However, boys who lost ambulation had significantly lower muscle function at baseline (North Star Ambulatory Assessment DMD-RA 23.6 vs. DMD-LA 18.8; p < 0.05). At baseline, healthy boys had significantly greater trabecular bone density at the distal radius /ulna (23%/27%) and distal tibia/fibula (30%/46%) than boys with DMD (p < 0.05). They also had significantly larger diaphyseal tibiae/fibulae (74%/36%) and radii/ulnae (49%/31%) with thicker corticies and consequently greater bone strength. In contrast, boys with DMD had greater cortical density (4%). Over time, there were small significant differences in the rate of change of both muscle and bone parameters between healthy boys and boys with DMD. For both ambulant and non-ambulant boys with DMD the greatest changes in cortical bone were evident at the tibia. After two years boys with DMD had on average, 63% less bone strength than healthy boys. However, the most strikingly significant difference was in trabecular bone density for boys who became non-ambulant. By 2 years non-ambulant DMD boys had 53% less trabecular bone density at distal tibia than their healthy age matched peers compared with boys who remained ambulant who had 27% less trabecular bone density. In conclusion, bone and muscle strength is reduced for all boys with DMD even while they remain ambulant. However, tibia trabecular bone density loss is significantly accelerated in DMD boys who lose independent ambulation compared to DMD boys who remain ambulant despite equivalent levels of corticosteroid exposure.

Peripheral quantitative computed tomography (pQCT) measures are associated with prior low trauma fracture in men.

Peripheral quantitative computed tomography (pQCT) assesses bone quantity and quality, complementary to current standard practice, and has potential to improve prediction of fracture risk. This study explored whether pQCT parameters were associated with prior fracture in men and found a number of parameters to be associated, particularly at the radius. PURPOSE: Peripheral quantitative computed tomography (pQCT) provides information about bone structure and density complementary to dual x-ray absorptiometry. This study aimed to determine which pQCT parameters are associated with prior fracture. METHODS: Participants were men (n = 508, age 33-96 years) from the Geelong Osteoporosis Study. Parameters at 4% (n = 469) and 66% (n = 436) of radial length, and 4% (n = 449) and 66% (n = 437) of tibial length were acquired (pQCT XCT 2000, Stratec Medizintechnik, Pforzheim, Germany), and mean standardised. Low trauma prior fractures in adulthood (≥ age 20 years) were radiologically confirmed when possible. Cross-sectional associations between pQCT and fracture were tested using logistic regression adjusting for confounders. RESULTS: Prior low trauma fractures were identified for 106 participants. Fracture was negatively associated with parameters at the 4% radius site: bone mass (adjusted OR = 0.67; 95%CI = 0.52-0.86), total density (OR = 0.61; 95%CI = 0.47-0.78), trabecular density (OR = 0.62; 95%CI = 0.48-0.79) and cortical subdensity (OR = 0.61; 95%CI = 0.47-0.77). At the 66% radius site, fracture was associated with total density (OR = 0.69; 95%CI = 0.55-0.87) and cortical thickness (OR = 0.68; 95%CI = 0.54-0.86). Fracture was associated with the ratio of the cortical area at the 66% site to the total area at the 4% site (OR = 0.74; 95%CI = 0.58-0.94). Prior fracture was negatively associated with parameters at the 4% tibial site: total density (OR = 0.67; 95%CI = 0.52-0.86), trabecular density (OR = 0.64; 95%CI = 0.50-0.82) and cortical subdensity (OR = 0.72; 95%CI = 0.56-0.92). Fracture was negatively associated with cortical density at the 66% site (OR = 0.74; 95%CI = 0.58-0.94), and the ratio of the cortical area at the 66% site to the total area at the 4% site (OR = 0.65; 95%CI = 0.46-0.91), but were attenuated in adjusted models. No other associations were identified. CONCLUSION: Prior fracture was associated with parameters at both the radius and tibia. This study highlights key pQCT parameters that may aid in the prediction of fracture risk.

The Effect of Bolus Vitamin D3 Supplementation on Distal Radius Fracture Healing: A Randomized Controlled Trial Using HR-pQCT.

Vitamin D is an important factor in bone metabolism. Animal studies have shown a positive effect of vitamin D3 supplementation on fracture healing, but evidence from clinical trials is inconclusive. A randomized controlled trial was performed to assess the effects of vitamin D3 supplementation on fracture healing using HR-pQCT-based outcome parameters. Thirty-two postmenopausal women with a conservatively treated distal radius fracture were included within 2 weeks postfracture and randomized to a low-dose (N = 10) and a high-dose (N = 11) vitamin D intervention group receiving a 6-week bolus dose, equivalent to 700 and 1800 IU vitamin D3 supplementation per day, respectively, in addition to a control group (N = 11) receiving no supplementation. After the baseline visit 1-2 weeks postfracture, follow-up visits were scheduled at 3-4, 6-8, and 12 weeks postfracture. At each visit, HR-pQCT scans of the fractured radius were performed. Cortical and trabecular bone density and microarchitectural parameters and microfinite element analysis-derived torsion, compression, and bending stiffness were assessed. Additionally, serum markers of bone resorption (CTX) and bone formation (PINP) were measured. Baseline serum levels of 25OHD3 were <50 nmol/L in 33% of all participants and <75 nmol/L in 70%. Compared with the control group, high-dose vitamin D3 supplementation resulted in a decreased trabecular number (regression coefficient ß: -0.22; p < 0.01) and lower compression stiffness (B: -3.63; p < 0.05, together with an increase in the bone resorption marker CTX (B: 0.062; p < 0.05). No statistically significant differences were observed between the control and low-dose intervention group. In conclusion, the bolus equivalent of 700 U/day vitamin D3 supplementation in a Western postmenopausal population does not improve distal radius fracture healing and an equivalent dose of 1800 IU/day may be detrimental in restoring bone stiffness during the first 12 weeks of fracture healing. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Pregnancy-Related Change in pQCT and Bone Biochemistry in a Population With a Habitually Low Calcium Intake.

In pregnancy, changes in maternal calcium (Ca) economy occur to satisfy fetal Ca demand. It is unclear whether maternal mineral reserves facilitate these requirements and no data exist from sub-Saharan Africa. The aim was to determine skeletal changes with peripheral quantitative computed tomography (pQCT) and bone biochemistry between early second and third trimesters. Pregnant rural Gambians aged 18 to 45 years (n = 467) participating in a trial of antenatal nutritional supplements (ISRCTN49285450) had pQCT scans and blood collections at mean (SD) 14 (3) and 31 (1) weeks' gestation. Outcomes were pQCT: radius/tibia 4% total volumetric bone mineral density (vBMD), trabecular vBMD, total cross-sectional area (CSA), 33%/38% radius/tibia cortical vBMD, bone mineral content (BMC), total CSA; biochemistry: collagen type 1 cross-linked ß-C-telopeptide (ß-CTX), type 1 procollagen N-terminal (P1NP), parathyroid hormone (PTH), and 1,25(OH)2 D. Independent t tests tested whether pooled or within-group changes differed from 0. Multiple regression was performed adjusting for age. Data for change are expressed as mean (confidence interval [CI] 2.5, 97.5%). Radius trabecular vBMD, cortical vBMD, and BMC increased by 1.15 (0.55, 1.75)%, 0.41 (0.24, 0.58)%, and 0.47 (0.25, 0.69)%. Tibia total and trabecular vBMD increased by 0.34 (0.15, 0.54)% and 0.46 (0.17, 0.74)%, while tibia cortical vBMD, BMC, and cortical CSA increased by 0.35 (0.26, 0.44)%, 0.55 (0.41, 0.68)% and 0.20 (0.09, 0.31)%, respectively. CTX, PTH, and 1,25(OH)2 D increased by 23.0 (15.09, 29.29)%, 13.2 (8.44, 19.34)%, and 21.0 (17.67, 24.29)%, while P1NP decreased by 32.4 (-37.19, -28.17)%. No evidence of mobilization was observed in the peripheral skeleton. Resorption, although higher in late versus early gestation, was lower throughout pregnancy compared with non-pregnant non-lactating (NPNL) in the same community. Formation was lower in late pregnancy than in early, and below NPNL levels. This suggests a shift in the ratio of resorption to formation. Despite some evidence of change in bone metabolism, in this population, with habitually low Ca intakes, the peripheral skeleton was not mobilized as a Ca source for the fetus. © 2021 crown copyright . Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). The article published with the permission of the Controller of HMSO and the Queen's Printer of Scotland..

Bone microarchitecture in patients with autoimmune hepatitis.

In patients with autoimmune hepatitis (AIH), osteoporosis represents a common extrahepatic complication, which we recently showed by an assessment of areal bone mineral density (aBMD) via dual-energy x-ray absorptiometry (DXA). However, it is well established that bone quality and fracture risk does not solely depend on aBMD, but also on bone microarchitecture. It is currently not known whether AIH patients exhibit a site-specific or compartment-specific deterioration in the skeletal microarchitecture. In order to assess potential geometric, volumetric, and microarchitectural changes, high-resolution peripheral quantitative computed tomography (HR-pQCT) measurements were performed at the distal radius and distal tibia in female patients with AIH (n = 51) and compared to age-matched female healthy controls (n = 32) as well as to female patients with AIH/primary biliary cholangitis (PBC) overlap syndrome (n = 25) and female patients with PBC alone (PBC, n = 36). DXA at the lumbar spine and hip, clinical characteristics, transient elastography (FibroScan) and laboratory analyses were also included in this analysis. AIH patients showed a predominant reduction of cortical thickness (Ct.Th) in the distal radius and tibia compared to healthy controls (p < .0001 and p = .003, respectively). In contrast, trabecular parameters such as bone volume fraction (BV/TV) did not differ significantly at the distal radius (p = .453) or tibia (p = .508). Linear regression models revealed significant negative associations between age and Ct.Th (95% confidence interval [CI], -14 to -5 µm/year, p < .0001), but not between liver stiffness, cumulative prednisolone dose (even after an adjustment for age), or disease duration with bone microarchitecture. The duration of high-dose prednisolone (≥7.5 mg) was negatively associated with trabecular thickness (Tb.Th) at the distal radius. No differences in bone microarchitecture parameters between AIH, AIH/PBC, and PBC could be detected. In conclusion, AIH patients showed a severe age-dependent deterioration of the cortical bone microarchitecture, which is most likely the major contribution to the observed increased fracture risk in these patients. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Effects of Combination Denosumab and High-Dose Teriparatide Administration on Bone Microarchitecture and Estimated Strength: The DATA-HD HR-pQCT Study.

In postmenopausal women at high risk of fracture, we previously reported that combined denosumab and high-dose (HD; 40 µg) teriparatide increased spine and hip bone mineral density (BMD) more than combination with standard-dose teriparatide (SD; 20 µg). To assess the effects of these combinations on bone microarchitecture and estimated bone strength, we performed high-resolution peripheral quantitative computed tomography (HR-pQCT) at the distal radius and distal tibia in these women, who were randomized to receive either teriparatide 20 µg (n = 39) or 40 µg (n = 37) during months 0 to 9 overlapped with denosumab 60 mg s.c. given at months 3 and 9, for a 15-month study duration. The 69 women who completed at least one study visit after baseline are included in this analysis. Over 15 months, increases in total BMD were higher in the HD-group than the SD-group at the distal tibia (5.3% versus 3.4%, p = 0.01) with a similar trend at the distal radius (2.6% versus 1.0%, p = 0.06). At 15 months, cortical porosity remained similar to baseline, with absolute differences of -0.1% and -0.7% at the distal tibia and -0.4% and -0.1% at the distal radius in the HD-group and SD-group, respectively; p = NS for all comparisons. Tibial cortical tissue mineral density increased similarly in both treatment groups (1.3% [p < 0.0001 versus baseline] and 1.5% [p < 0.0001 versus baseline] in the HD-group and SD-group, respectively; p = 0.75 for overall group difference). Improvements in trabecular microarchitecture at the distal tibia and estimated strength by micro-finite element analysis at both sites were numerically greater in the HD-group compared with SD-group but not significantly so. Together, these findings suggest that short-term treatment combining denosumab with either high- or standard-dose teriparatide improves HR-pQCT measures of bone density, microstructure, and estimated strength, with greater gains in total bone density observed in the HD-group, which may be of benefit in postmenopausal women with severe osteoporosis. © 2020 American Society for Bone and Mineral Research (ASBMR).

Bone grafiting combined with Sauvé-Kapandji Procedures for the treatment of aseptic distal radius non-union.

Distal radius fractures are the most common type of upper limb fractures in adults. Non-union after distal radius fracture is rare, serious and unpredictable. The aim of our paper is to analyse the clinical and radiological outcomes of bone grafting and Sauvé-Kapandji Procedures for the treatment of aseptic distal radius non-union. We enrolled 13 patients with distal radius aseptic non-union. The following parameters were evaluated: The surgical time, elbow, forearm and wrist range of motion, the subjective quality of life and the wrist function measured by Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH), Pain Visual Analogic Score (VAS) and the complication rate. Bone union was measured using the radiographic union score as described by Radiographic Union Score (RUS). The evaluation endpoint was set at 24 months after surgery. All patients achieved fracture union. Grip strength improved by 12.4 kg. There was also improvement in wrist flexion, in wrist extension, and forearm pronosupination. These ranges of motion and grip strength improvements were statistically significant. Only 6 patients returned to full activity. This surgical technique represents a reliable alternative for treatment of distal radius aseptic non-unions. Further studies are needed to assess the long-term clinical results of this surgical procedure.

Severe bone microarchitecture deterioration in a family with hereditary neuropathy: evidence of the key role of the mechanostat.

In this report, we present three cases of individuals from the same family with a diagnosis of CMT with severe tibia bone microarchitecture deterioration assessed by HR-pQCT. Charcot-Marie-Tooth disease (CMT) or hereditary neuropathy involves both motor and sensory nerves. Falls are often the first manifestation in these patients and represent an important risk factor for fracture. The reduction of mechanical input on bone inhibits bone formation by osteoblasts and accelerates bone resorption by osteoclasts, leading to disuse osteoporosis. We report three cases of individuals from the same family with a diagnosis of CMT with severe tibia bone microarchitecture deterioration assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT). This affectation was exclusive to the tibia; the radius remained undamaged, showing the consequences of the lack of mobility and mechanical stimulation. Physical activity and rehabilitation, in addition to adequate calcium and vitamin D supplementation, may play an essential role in the management of this disease.

Wrist Joint Skeletal Changes in Children With Transfusion-dependent Thalassemia.

BACKGROUND: Arthropathies and bone deformities are well known to occur in patients with thalassemia major and have been attributed to the disease or to its therapy. Before the advent of chelation therapy, these children developed widened diploic space and "hair-on-end" pattern in skull, "cobweb" pattern in the pelvis, and the lack of the normal concave outline in the long bones because of extensive marrow proliferation. After the introduction of iron-chelation therapy, these patients were noted to develop metaphyseal abnormalities and vertebral changes resembling spondylo-metaphyseal dysplasia. Only one study has shown some association of deferiprone (chelating agent) use with distal ulnar changes in these children. Our study was done to describe the skeletal changes and deformities in wrist joints of children with transfusion-dependent thalassemia and correlate them with age, mean pretransfusion hemoglobin level, mean serum ferritin level, and type and duration of chelation therapy in these children. METHODS: A total of 60 children with transfusion-dependent thalassemia from the thalassemia daycare center were examined. These children were divided into 3 groups on the basis of their age (group A: 2 to 6 y, group B: 6 to 10 y, and group C: 10 to 14 y). Detailed history, including treatment history, number of blood transfusions received over the last 1 year, clinical examination, and radiologic assessment of both forearm with wrists were done. RESULTS: The clinical and radiologic differences in radial and ulnar lengths increased significantly with the increasing age of these patients, the ulna being short. There was some correlation between increasing negative ulnar variance and distal radial articular angle with deferiprone consumption. CONCLUSION: Chelation therapy, particularly with deferiprone, may cause distal ulnar growth arrest causing ulnar shortening and progressive radial bowing in these children. LEVEL OF EVIDENCE: Level IV-case series.