Site specific differences in vBMD and geometry in postmenopausal women with primary hyperparathyroidism.

PURPOSE: Primary Hyperparathyroidism (PHPT) is associated with catabolic effects at both trabecular and cortical bone. Mechanical loading is one of the most important natural anabolic stimuli for bone at all ages. The present study was designed to assess the impact of PHPT on vBMD and bone geometry using peripheral quantitative computed tomography (pQCT) at the radius and tibia, sites with similar structural characteristics, but subject to different loading conditions. METHODS: We evaluated the impact of PHPT on bone, by comparing the z-scores of volumetric Bone Mineral Density (vBMD) and indices of bone geometry simultaneously at the tibia and the radius by pQCT, skeletal sites with similar structure, but subject to different loading conditions. Forty-one postmenopausal women with PHPT and 79 controls, comprised the study group. RESULTS: At both trabecular and cortical sites, vBMD and bone geometry indices were significantly lower in patients compared with controls. In patients with PHPT, apart from a lower z-score for total vBMD (p = 0.01) at the radius, there was no other difference between the radius and the tibia at the trabecular sites. On the contrary, at cortical sites, the z-scores of cortical bone mineral content (p = 0.02), cortical vBMD (p = 0.01) and cortical cross-sectional area (p = 0.05) were significantly lower at the radius compared with the tibia, indicating that cortical bone at the weight bearing tibia might be less affected by the catabolic actions of continuous parathyroid hormone (PTH) exposure. PTH levels were positively associated with the difference in z-scores of cort BMD (r = 0.439, p < 0.01) indicating that in more severe cases, as expressed by higher PTH levels, the deleterious effects at the non-weight bearing radius might be accentuated. CONCLUSION: We found that in postmenopausal women with PHPT, both trabecular and cortical bone are adversely affected. However, at the weight bearing tibia as compared with the radius, the deleterious effects, especially on cortical bone, seem to be attenuated. TRIAL REGISTRATION NUMBER: NCT05426512, 21/06/2022, "retrospectively registered".

Shifting from open to video-assisted parathyroidectomy: effect of the adjustment period on safety, clinical outcomes and cost.

INTRODUCTION: Bilateral neck exploration (BNE) has been the gold standard for the treatment of primary hyperparathyroidism (PHPT). Minimally invasive parathyroidectomy (MIP) has emerged as an alternative procedure for localised solitary adenomas. The most popular MIP techniques are the open MIP (OMIP) and the minimally invasive video-assisted parathyroidectomy (MIVAP). This study aims to assess whether we achieved a smooth transition from OMIP to MIVAP without compromising the results or increasing the cost. METHODS: A parathyroid adenoma was successfully localised preoperatively in 77/86 patients with PHPT. MIP was contraindicated in 27/86 cases. For MIVAP, a 5mm, 30 degree camera was employed, along with special instruments. RESULTS: Median preoperative parathyroid hormone (PTH) level was 145.9pg/dl (59-2,151) and median calcium (Ca) was 10.8mg/dl (9.3-19). Comparing MIVAP (N=31) with OMIP (N=28), there was no significant difference in the age, sex, location of the adenoma, preoperative PTH and Ca levels as well as in all the other factors compared, apart from the size of adenomas, which were bigger in the OMIP group (1.85cm vs 1.4cm, p=0.032). Moreover, cure rates, operating time, hospital stay and rates of postoperative normocalcaemia were similar between the two groups. CONCLUSIONS: Despite the learning curve, MIVAP was not found to be inferior to OMIP for localised adenomas. The final cost was no higher for MIVAP than OMIP with the use of common reusable instruments. This, along with surgeons' experience in parathyroid and endoscopic surgery facilitates a smooth and cost-effective transition from OMIP to MIVAP.

A Multicenter Study to Evaluate Harmonization of Assays for C-Terminal Telopeptides of Type I Collagen (ß-CTX): A Report from the IFCC-IOF Committee for Bone Metabolism (C-BM).

BACKGROUND: Biochemical bone turnover markers are useful tools to assess bone remodeling. C-terminal telopeptide of type I collagen (ß-CTX) has been recommended as a reference marker for bone resorption in research studies. METHODS: We describe the results of a multicenter study for routine clinical laboratory assays for ß-CTX in serum and plasma. Four centers (Athens GR, Copenhagen DK, Liege BE and Sheffield UK) collected serum and plasma (EDTA) samples from 796 patients presenting to osteoporosis clinics. Specimens were analyzed in duplicate with each of the available routine clinical laboratory methods according to the manufacturers' instructions. Passing-Bablok regressions, Bland-Altman plots, V-shape evaluation method, and Concordance correlation coefficient for ß-CTX values between serum and plasma specimens and between methods were used to determine the agreement between results. A generalized linear model was employed to identify possible variables that affected the relationship between the methods. Two pools of serum were finally prepared and sent to the four centers to be measured in 5-plicates on 5 consecutive days with the different methods. RESULTS: We identified significant variations between methods and between centers although comparison results were generally more consistent in plasma compared to serum. We developed univariate linear regression equations to predict Roche Elecsys®, IDS-iSYS, or IDS ELISA ß-CTX results from any other assay and a multivariable model including the site of analysis, the age, and weight of the patient. The coefficients of determination (R2) increased from approximately 0.80 in the univariate model to approximately 0.90 in the multivariable one, with the site of analysis being the major contributing factor. Results observed on the pools also suggest that long-term storage could explain the difference observed with the different methods on serum. CONCLUSION: Our results show large within- and between-assay variation for ß-CTX measurement, particularly in serum. Stability of the analyte could be one of the explanations. More studies should be undertaken to overcome this problem. Until harmonization is achieved, we recommend measuring ß-CTX by the same assay on EDTA plasma, especially for research purposes in large pharmacological trials where samples can be stored for long periods before they are assayed.

Comparative effects of denosumab or bisphosphonate treatment on bone mineral density and calcium metabolism in postmenopausal women.

OBJECTIVES: To clarify potential differences between denosumab (DNS) and bisphosphonates (BIS) in terms of bone density and bone metabolism, in a sample of postmenopausal women. METHODS: A total of 113 postmenopausal women aged 53-66 years were treated with either DNS or BIS for 12 months. Bone densitometry and laboratory tests were compared between baseline and follow-up. RESULTS: Femoral neck BMD increased in both treatment-arms (FN-BMD, DNS: 0.69±0.07 g/cm2 to 0.75±0.09 g/cm2; BIS: 0.69±0.06 g/cm2 to 0.71±0.07 g/cm2; p≤0.001 in both cases). Lumbar spine BMD (LS-BMD) increased significantly only in the DNS-group (0.83±0.14 g/cm2 to 0.89±0.14 g/cm2, p=0.0001). Only women under treatment with DNS had a significant increase in serum parathyroid hormone (PTH: 44.87±17.54 pg/mL to 53.27±15.77 pg/mL, p=0.04), independently of baseline vitamin D levels. DNS-administration resulted in higher increase from baseline in FN-BMD compared to BIS (DNS vs BIS: 8.7%±8.5 vs 3.8%±7.3, p=0.004). Finally, baseline 25OH vitamin D levels did not determine the extent of PTH-increase following administration of DNS- or BIS-treatment. CONCLUSIONS: Both treatments increased BMD, however, the effect of DNS on FN-BMD was superior compared to that of BIS. DNS-treatment increased serum PTH. Baseline 25OH vitamin D levels did not predict the extent of PTH increase at follow-up.

Thalassemia-associated osteoporosis: a systematic review on treatment and brief overview of the disease.

Thalassemia-associated osteoporosis constitutes a major complication in patients with thalassemia. This review presents the existing studies on the treatment of thalassemia-associated osteoporosis and discusses the management of this debilitating complication. A brief presentation of the disease characteristics and pathogenetic mechanisms is also provided. The life expectancy of patients with thalassemia has increased markedly in recent years resulting in the aging of the population and the emergence of new comorbidities. The majority of patients with thalassemia have low bone mineral density and experience lifelong fracture rates as high as 71 %. The pathogenesis of thalassemia-associated osteoporosis (TAO) is multifactorial with anemia and iron overload playing crucial role in its development. Data concerning the prevention and treatment of TAO are extremely limited. We performed a literature research in Pubmed and Scopus to identify interventional studies evaluating the effects of various agents on TAO. Seventeen studies were retrieved. We present the results of these studies as well as a brief overview of TAO including presentation, pathogenesis, and management. Most of the studies identified are of poor quality, are not randomized controlled, and include small number of participants. There are no data concerning effects on fracture rates. Bisphosphonates are the most widely studied agents and among them zoledronic acid is the most well studied. Hormone replacement treatment (HRT) shows beneficial but small effects. Denosumab and strontium ranelate have each been evaluated in only a single study, while there are no data about the effects of anabolic agents. Given the increased life expectancy and the increase in fracture rates with age, more data about the management of TAO are warranted. Moreover, due to the need for lifelong management starting at young age, careful treatment plans which may include sequential treatment may often be required. However, currently, there are no relevant data available.

Atypical femoral fracture in a beta-thalassemia major patient with previous bisphosphonate use: case report and a review of the literature.

There are numerous studies presenting the beneficial effect of bisphosphonates (BPs) on bone disease of patients suffering from beta-thalassemia major (TM). Although BPs have been widely used, adverse events have been described including atypical femoral fractures (AFF). In the present case, a male adult patient suffering from TM sustained an AFF fulfilling all major and two minor criteria. Before AFF, the patient had been treated with zoledronic acid for three years and remained another one year without osteoporosis therapy. To our knowledge, this is the first reported case of AFF in a patient suffering from TM, probably due to the small sample size of patients with thalassemia. The purpose of the present case is to increase the awareness amongst haematologists, who mainly deal with TM patients, of the adverse events of BP use.

Management of bisphosphonate-related osteonecrosis of the jaw: a literature review.

Osteonecrosis of the jaw (ONJ) is a serious side effect of bisphosphonate use in patients with osteoporosis, Paget's disease, hypercalcemia of malignancy, metastatic bone disease and multiple myeloma, although recently this complication has also been reported in patients under non-bisphosphonate medication, such as denosumab and bevacizumab. The occurrence of ONJ is higher in oncology patients treated with high-dose iv bisphosphonates than in osteoporosis patients treated with oral bisphosphonates. Although multiple hypotheses have been proposed, the exact pathogenic mechanism of ONJ still remains unclear. As treatment protocols based on randomized controlled trials (RCTs) do not exist, we critically reviewed the existing data concerning the management of bisphosphonate-related osteonecrosis of the jaw, including the most recent data for the use of teriparatide and hyperbaric oxygen.

Decreased tibial bone strength in postmenopausal women with aseptic loosening of cemented femoral implants measured by peripheral quantitative computed tomography (pQCT).

Aseptic loosening after total hip arthroplasty is related to bone loss of the operated leg. The aim of the present study was to investigate the effect of aseptic loosening on volumetric bone mineral density (vBMD) and bone geometry in the operated leg, in postmenopausal women with a loosened cemented femoral implant using peripheral quantitative computed tomography (pQCT). We matched 12 postmenopausal women with aseptic loosening of cemented femoral implant, with 12 women without aseptic loosening (control group) according to age, BMI, and years from operation. All patients underwent pQCT of both tibias, DXA of the lumbar spine, and determination of biochemical markers of bone turnover. pQCT values in the control group as well as the nonoperated legs between groups had no significant difference. In the aseptic loosening group, there was significant reduction of cortical vBMD (cort vBMD) at 14% and 38% sites (cortical site), cortical thickness at 38% site, and of polar stress strength index (SSIp) at 14% site (transition zone) in the operated compared with the nonoperated leg. Similarly, there was significant reduction of cort vBMD at 14% and 38% sites and total vBMD and trabecular vBMD (trab vBMD) at the 14% site in the operated legs between the two groups. The aseptic loosening group had increased osteocalcin and serum collagen cross-linked N- and C-telopeptides (sNTX and sCTX) levels compared with controls. Aseptic loosening is associated with significant decrease of cortical and trabecular vBMD, and impairment of bone geometry and strength only in the operated leg. Increased bone turnover probably represents a local phenomenon, and is not associated with systemic skeletal disease.

Effect of rhythmic gymnastics on volumetric bone mineral density and bone geometry in premenarcheal female athletes and controls.

CONTEXT AND OBJECTIVE: Weight-bearing exercise during growth exerts positive effects on the skeleton. Our objective was to test the hypothesis that long-term elite rhythmic gymnastics exerts positive effects on volumetric bone mineral density and geometry and to determine whether exercise-induced bone adaptation is associated with increased periosteal bone formation or medullary contraction using tibial peripheral quantitative computed tomography and bone turnover markers. DESIGN AND SETTING: We conducted a cross-sectional study at a tertiary center. SUBJECTS: We studied 26 elite premenarcheal female rhythmic gymnasts (RG) and 23 female controls, aged 9-13 yr. MAIN OUTCOME MEASURES: We measured bone age, volumetric bone mineral density, bone mineral content (BMC), cortical thickness, cortical and trabecular area, and polar stress strength index (SSIp) by peripheral quantitative computed tomography of the left tibia proximal to the distal metaphysis (trabecular) at 14, 38 (cortical), and 66% (muscle mass) from the distal end and bone turnover markers. RESULTS: The two groups were comparable according to height and chronological and bone age. After weight adjustment, cortical BMC, area, and thickness at 38% were significantly higher in RG (P < 0.005-0.001). Periosteal circumference, SSIp, and muscle area were higher in RG (P < 0.01-0.001). Muscle area was significantly associated with cortical BMC, area, and SSIp, whereas years of training showed positive association with cortical BMC, area, and thickness independent of chronological age. CONCLUSIONS: RG in premenarcheal girls may induce positive adaptations on the skeleton, especially in cortical bone. Increased duration of exercise is associated with a positive response of bone geometry.

Improvement in bone strength parameters. The role of strontium ranelate.

Strontium ranelate (SR) is a novel anti-osteoporotic agent approved for the treatment of postmenopausal osteoporosis. SR appears to reduce bone resorption by decreasing osteoclast differentiation and activity, and to stimulate bone formation by increasing replication of pre-osteoblast cells, leading to increased matrix synthesis. The effect of SR on bone strength indices has been investigated in several animal models, including intact female and male rats, ovariectomized rats, after rat limb immobilization and in monkeys. In intact female rats, SR significantly improved bone mechanical properties of vertebrae and midshaft femur. The improvement in bone mechanical properties was characterized by an increase in maximal load and in energy to failure, which was due to an increment in plastic energy. These results suggest that new bone formed following strontium ranelate treatment is able to withstand greater deformation before fracture. Moreover, in ovariectomized rats, a model that resembles postmenopausal osteoporosis, 1-year exposure to strontium ranelate significantly prevented alteration of bone mechanical properties of vertebrae in association with a partial preservation of the trabecular microarchitecture. Finally after limb immobilization SR prevented microarchitectual deterioration, while no significant alteration was observed in crystal characteristics and degree of mineralization after SR administration in monkeys.

Strontium ranelate: a novel treatment in postmenopausal osteoporosis.

Strontium ranelate (SR) is a novel antiosteoporotic agent, electively concentrated in positions of active bone formation, and especially onto the crystal surface that allows permanent exchanges with extracellular fluid. Although the mechanism(s) of action is still under rigorous research, SR appears to reduce bone resorption by decreasing osteoclast differentiation and activity and to stimulate bone formation by increasing replication of preosteoblast cells, leading to increased matrix synthesis. In the placebo-controlled, phase III trial spinal osteoporosis therapeutic intervention (SOTI) (no=1442; mean age 69 years), there was a 41% decrease over 3 years in the number of patients with new vertebral fractures in the SR (2 g/day) group versus placebo (P<0.001), already detected after 12 months (49% lower risk, P<0.001). The phase III treatment of peripheral osteoporosis (TROPOS) study assessed the efficacy of SR (2 g/day) in preventing nonvertebral fractures in postmenopausal osteoporosis (no=4932; mean age 77 years). SR reduced nonvertebral fracture risk by 16% versus placebo (P=0.04) and hip fracture risk by 36% (P=0.031) in osteoporotic patients older than 74 years. Thus SR is an effective and safe treatment for vertebral and hip osteoporosis with a unique mode of action.