PLS3 Mutations in X-Linked Osteoporosis: Clinical and Genetic Features in Five New Families.

Childhood-onset osteoporosis is a rare but clinically significant condition. Studies have shown pathogenic variants in more than 20 different genes as causative for childhood-onset primary osteoporosis. The X-chromosomal PLS3, encoding Plastin-3, is one of the more recently identified genes. In this study, we describe five new families from four different European countries with PLS3-related skeletal fragility. The index cases were all hemizygous males presenting with long bone and vertebral body compression fractures. All patients had low lumbar spine bone mineral density (BMD). The age at the first clinical fracture ranged from 1.5 to 13 years old. Three of the identified PLS3 variants were stop-gain variants and two were deletions involving either a part or all exons of the gene. In four families the variant was inherited from the mother. All heterozygous women reported here had normal BMD and no bone fractures. Four patients received bisphosphonate treatment with good results, showing a lumbar spine BMD increment and vertebral body reshaping after 10 months to 2 years of treatment. Our findings expand the genetic spectrum of PLS3-related osteoporosis. Our report also shows that early treatment with bisphosphonates may influence the disease course and reduce the progression of osteoporosis, highlighting the importance of early diagnosis for prompt intervention and appropriate genetic counseling.

Vitamin D and vitamin K status in postmenopausal women with normal and low bone mineral density.

OBJECTIVES: Vitamin D and K are believed to promote bone health, but existing evidence is controversial. This study aimed to measure several metabolites of both vitamins by liquid chromatography tandem mass spectrometry (LC-MS/MS) in a cohort of postmenopausal women with low and normal bone mineral density (BMD). METHODS: Vitamin metabolites (25-hydroxyvitamin D (25[OH]D), 24,25-dihydroxyvitamin D (24,25(OH)2D), phylloquinone (K1), menaquinone-4 (MK-4) and MK-7) were measured in 131 serum samples by LC-MS/MS. The vitamin D metabolite ratio (VMR) was calculated. Parathyroid hormone (PTH), type I procollagen-N-terminal-peptide (PINP) and C-terminal telopeptides of type I collagen (CTX-I) were measured by immunoassay. Dual X-ray absorptiometry was performed to identify participants with normal (T-score>-1) and low (T-score<-1) BMD. RESULTS: Mean age was 58.2±8.5 years. BMD was normal in 68 and low in 63 women. Median (interquartile range) for 25(OH)D and total vitamin K concentrations were 53.5 (39.6-65.9) nmol/L and 1.33 (0.99-2.39) nmol/L. All vitamin metabolites were comparable in individuals with normal and low BMD. Furthermore, BMD and trabecular bone score were comparable in participants with adequate and inadequate vitamin status (at least one criterion was met: 25(OH)D <50 nmol/L, 24,25(OH)2D <3 nmol/L, VMR <4 %, total vitamin K <0.91 nmol/L). PTH, but not PINP or CTX-I, was inversely correlated with 25(OH)D, 24,25(OH)2D and VMR. Synergistic effects between vitamin D and K were not observed. CONCLUSIONS: Vitamin D and K status is not related to BMD and trabecular bone quality in postmenopausal women. Inverse associations were only seen between vitamin D metabolites and PTH.

Effect of Calcium and Vitamin D Supplementation With and Without Collagen Peptides on Volumetric and Areal Bone Mineral Density, Bone Geometry and Bone Turnover in Postmenopausal Women With Osteopenia.

Collagen peptides (CPs) have been shown to potentially have a role as a treatment option in osteopenia. In the present randomized prospective study, we examined the effect of calcium, vitamin D with and without CPs supplementation on changes in volumetric bone mineral density (vBMD) and bone geometry assessed by peripheral quantitative computed tomography at the tibia, areal bone mineral density (aBMD) assessed by dual-energy X-ray absorptiometry at the lumbar spine and the hip and bone turnover markers over 12-mo. Fifty-one postmenopausal women with osteopenia were allocated to Group A who received orally 5 g CPs, 500 mg calcium and 400 IU vitamin D3 and Group B who received the same dose of calcium and vitamin D3 per day. The primary endpoint was the change of trabecular bone mineral content (BMC) and vBMD after 12-mo supplementation in Groups A and B. At the trabecular site (4% of the tibia length), Group A had a significant increase of total BMC by 1.96 ± 2.41% and cross-sectional area by 2.58 ± 3.91%, trabecular BMC by 5.24 ± 6.48%, cross-sectional area by 2.58 ± 3.91% and vBMD by 2.54 ± 3.43% and a higher % change of these parameters at 12 mo in comparison to Group B (p < 0.01, p = 0.04, p < 0.01, p = 0.04, p = 0.02, respectively). At the cortical site (38% of the tibia length), total and cortical vBMD increased by 1.01 ± 2.57% and 0.67 ± 1.71%. Furthermore, the mean aBMD at the spine was higher (p = 0.01), while bone markers decreased in Group A compared to Group B. The present study shows improvement of trabecular and cortical parameters as assessed by peripheral quantitative computed tomography at the tibia, prevention of aBMD decline and decrease of bone turnover after 12-mo supplementation with calcium, vitamin D with CPs.

Teriparatide Treatment in Patients with Pregnancy- and Lactation-Associated Osteoporosis.

Pregnancy- and lactation-associated osteoporosis (PLO) is a rare disease, presenting in most cases with severe back pain due to low energy vertebral fractures (VFs). Our purpose was to assess the effect of teriparatide (TPTD) vs. conventional management on areal bone mineral density (aBMD) and trabecular bone score (TBS) in patients with PLO. A multicenter retrospective cohort study concerning premenopausal women with PLO. Nineteen women were treated with TPTD (20 µg/day) (group A) plus calcium and vitamin D and eight women with calcium and vitamin D only (group B) for up to 24 months. The primary end-point was between group differences in lumbar spine (LS) and total hip (TH) aBMD, and TBS at 12 and 24 months. Patients in group A had sustained a median of 4.0 VFs (3-9) vs. 2.5 VFs (1-10) in group B (p = 0.02). At 12 months, patients on TPTD vs. controls achieved a mean aBMD increase of 20.9  ±  11.9% vs. 6.2  ±  4.8% at the LS (p < 0.001), 10.0  ±  11.6% vs. 5.8  ±  2.8% at the TH (p = 0.43), and 6.7  ±  6.9% vs. 0.9  ±  3.7% in TBS (p = 0.09), respectively. At 24 months, seven patients on TPTD and six controls achieved a mean LS aBMD increase of 32.9  ±  13.4% vs. 12.2  ±  4.2% (p = 0.001). P1NP levels during the first month of TPTD treatment were positively correlated with the 1-year LS aBMD change (r = 0.68, p = 0.03). No new clinical fractures occurred while on-treatment. In patients with PLO, TPTD treatment resulted in significantly greater increases in LS aBMD compared with calcium and vitamin D supplementation at 12 and 24 months.

Efficacy of Antiosteoporotic Medications in Patients With Rebound-Associated Fractures After Denosumab Discontinuation.

Denosumab discontinuation results in rapid bone loss and increased risk of multiple rebound-associated vertebral fractures (RAVFs). The optimal treatment for patients who have sustained such fractures is currently unknown. We aimed to investigate the bone mineral density (BMD) changes achieved with various regimens in postmenopausal women who had sustained RAVFs after denosumab discontinuation in everyday clinical practice. In this multicenter, retrospective observational study, 39 Greek postmenopausal women from six regional bone centers throughout Greece with RAVFs after denosumab discontinuation were included. We collected BMD and fracture data before and 1 year after treatment with denosumab (n = 20), teriparatide (n = 8), zoledronate (n = 8) or teriparatide/denosumab combination (n = 3). Both lumbar spine (LS)-- and femoral neck (FN)-BMD were preserved with all regimens used. With the exception of zoledronate, a trend towards increase was observed with all regimens in LS-BMD. Three patients sustained additional fractures despite treatment reinstitution (2 with zoledronate and 1 with teriparatide). Among patients with RAVFs following denosumab discontinuation both antiresorptive (zoledronate and denosumab) and anabolic (teriparatide) treatment as well as the combination of denosumab with teriparatide seem to be effective in terms of BMD response.

Progression of Rebound-Associated Vertebral Fractures Following Denosumab Discontinuation Despite Reinstitution of Treatment: Suppressing Increased Bone Turnover May Not Be Enough.

Rebound-associated vertebral fractures (RAVFs) could occur in a minority of the patients who discontinue denosumab. In such patients, denosumab is often reinstituted to rapidly suppress bone turnover and avert the risk of additional fractures. Herein we report the cases of 2 patients who sustained RAVFs, and in whom resuming denosumab treatment did not avert the occurrence of new RAVFs a few months later, despite the suppression of bone turnover markers. It seems that denosumab reinstitution cannot completely eliminate the risk of new RAVFs and that the rebound of bone turnover may not be the sole mechanism to explain this phenomenon.

Adult hypophosphatasia treated with reduced frequency of teriparatide dosing.

We report a 41-year-old man diagnosed with the adult form of hypophosphatasia (HPP) and treated for 4 years with less frequent than conventional daily doses of teriparatide (TPTD). He presented with a history of three low-energy fractures and low bone mineral density (BMD) ineffectively treated with bisphosphonate. We identified within ALPL, the gene that encodes the homodimeric "tissue-nonspecific" isoenzyme of alkaline phosphatase (ALP) and underlies HPP, a heterozygous missense mutation (c.455 G>A→R135H). Characteristic painful periarticular calcification removed at a shoulder did not recur. However, access to medical treatment with asfotase alfa (AA) was denied. After he sustained a low-energy metatarsal fracture, we administered TPTD subcutaneously "off-label" at 20 µg/d. An elbow fracture occurred two months later. Five months afterwards, due to his limited number of approved TPTD doses, TPTD treatment was extended using alternate-day dosing. Although his serum ALP activity did not increase (33-48 U/l; reference range 40-120) with 4 years of TPTD treatment, his BMD improved 15% in the lumbar spine and 6% in the femoral neck with no further fractures. Our experience represents success overcoming two prescription deadlocks; AA was denied for adult HPP, and TPTD was not to be administered daily for more than two years.

Does Vitamin D affects changes in volumetric bone mineral density and architecture in postmenopausal women after conservatively treated distal radius fractures?

OBJECTIVE: We examined the role of vitamin D on volumetric bone mineral density (vBMD) and architecture during the first week's post-fracture in postmenopausal women (PMW) with distal radial fractures (DRF) treated conservatively using peripheral Quantitative Computed Tomography (pQCT). METHODS: Patients were classified into 2 groups according to initial median 25(OH)D level; Group A (25(OH)D ≥15 ng/ml) and group B (25(OH)D <15 ng/ml). All patients were followed for 12 weeks at three visits: baseline, 6 weeks and 12 weeks post fracture. pQCT was performed at baseline in fractured and contralateral non-fractured radius and at 6th and 12th week on the fractured side. RESULTS: 39 patients completed the protocol. Mean 25(OH)D levels were 15.60±7.35 ng/ml (3.5-41.7). Trabecular (trab) bone mineral content (BMC) and trabvBMD increased at 6 wk. vs. baseline (p<0.001). Cortical BMC, cortvBMD and cross- sectional area (CSA) progressively decreased (p<0.001) during the 12 weeks. There was no interaction between baseline 25(OH)D levels and changes in trabecular and cortical BMC, vBMD and CSA. Advanced age and higher CTX and P1NP were associated with higher cortical bone loss. CONCLUSION: Vitamin D deficiency does not affect the early architectural changes after a DRF. Advanced age and higher bone remodeling were associated with higher cortical bone loss, probably related to immobilization and independent of vitamin D levels.

Fibroblast Growth Factor 23 (FGF23) and Klotho Protein in Beta-Thalassemia.

Derangements in phosphate and calcium homeostasis are common in patients with beta-thalassemia. Fibroblast growth factor 23 (FGF23) is among the main hormones regulating phosphate levels, while several studies underline an interplay between iron (Fe) and FGF23. Herein, we investigated, for the first time, the serum intact molecule (iFGF23) and the carboxyl-terminal fragment (C-FGF23) and Klotho levels simultaneously in patients with beta-thalassemia major receiving iron chelation regimens in comparison to healthy control subjects. We also correlated them with the body iron burden. The observational case-control study included 81 subjects (40 thalassemic patients and 41 healthy controls). Serum iFGF23, C-FGF23 and Κlotho were measured by ELISA. Parathormone, 25-hydroxycholecalciferol, calcium, and phosphorus were measured in blood and/or urine. The degree of hemosiderosis was evaluated by assessing the serum ferritin levels and performing T2* MRI measurements. Serum C-FGF23 levels were significantly lower in patients compared to control subjects (p=0.04), while iFGF23 and Klotho levels did not differ. Serum C-FGF23 levels were negatively correlated with ferritin (r=-0,421, p=0.018), whereas there were no significant correlations of each of the three factors with the iron chelation therapy. Decreased serum C-FGF23 levels were found in ßTh patients which may be attributed to inhibition of proteolytic cleavage of iFGF23. Further studies in a greater number of patients will shed more light on the disturbances of the iFGF23, Klotho and C-FGF23 in thalassemia and their possible role in bone disease of such patients.

Effectiveness of intramuscular ergocalciferol treatment in a patient with osteomalacia and insufficiency fractures due to severe vitamin D deficiency after bariatric surgery.

Vitamin D (vitD) deficiency and bone loss may occur after bariatric surgery and hence, supplementation with high oral doses of vitD may be required. Alternatively, intramuscular depot ergocalciferol, which slowly releases vitD and bypasses the gastrointestinal tract, could be administrated. We present a case of severe vitD deficiency-osteomalacia after gastric bypass operation for morbid obesity, treated with ergocalciferol intramuscularly. A 45-year-old woman was presented with hip pain and muscle weakness, which led ultimately to immobilization in a wheelchair. Fifteen years ago, she underwent roux-en-Y gastric by-pass for morbid obesity. Occasionally, she was treated with multivitamin supplements. On admission, iron deficiency anaemia, vitD deficiency (25OHD: 3.7 ng/ml) and secondary hyperparathyroidism were revealed. Bone turnover markers (BTM) were elevated. Radiological evaluation demonstrated insufficiency fractures on the pubic and left femur and reduced BMD. Osteomalacia due to vitD deficiency and calcium malabsorption were diagnosed. Calcium citrate 500 mg qid and intramuscular ergocalciferol 600,000 IU every 20 days were initiated. One month later, musculoskeletal pain and weakness were resolved and the patient was mobilized. Few months later, vitD, BTM and BMD showed substantial improvement. Intramuscular ergocalciferol administration can improve the clinical and biochemical status and thus, is suggested to prevent and/or treat osteomalacia in such patients.

Effect of calcium and vitamin D supplementation with and without collagen peptides on bone turnover in postmenopausal women with osteopenia.

OBJECTIVES: Collagen peptides (CPs) seem to exert beneficial effects on bone and may have a role as a treatment option. In the present randomized prospective study, we aimed to examine the efficacy, as expressed by changes in P1NP and CTX, and the tolerability of 3-month supplementation of calcium, vitamin D with or without bioactive CPs in postmenopausal women with osteopenia. METHODS: Fifty-one female, postmenopausal women with osteopenia were allocated to two groups: Group A received a sachet containing 5 g CPs, 3.6 g calcium lactate (equivalent to 500 mg of elemental calcium) and 400 IU vitamin D3 and group B received a chewable tablet containing 1.25 g calcium carbonate (equivalent to 500 mg of elemental calcium) and 400 IU vitamin D3 daily. RESULTS: In group A, the P1NP levels significantly decreased by 13.1% (p<0.001) and CTX levels decreased by 11.4% (p=0.058) within 3 months of supplementation. In group B, P1NP and CTX did not change. Group A presented better compliance in comparison to group B and no adverse events contrary to group B. CONCLUSIONS: These findings may reflect the reduction of the increased bone turnover in postmenopausal women with the use of calcium, vitamin D and CPs supplements. The addition of CPs in a calcium and vitamin D supplement may enhance its already known positive effect on bone metabolism. Clinical Trial ID: NCT03999775.

A multicenter study to evaluate harmonization of assays for N-terminal propeptide of type I procollagen (PINP): a report from the IFCC-IOF Joint Committee for Bone Metabolism.

Background Biochemical bone turnover markers (BTM) are useful tools to assess bone remodeling at the cellular level. N-terminal propeptide of type I procollagen (PINP) has been recommended as a reference marker for bone formation in research studies. Methods We describe the results of a multicenter study for routine clinical laboratory assays for PINP in serum and plasma. Four centers (Athens, Greece [GR], Copenhagen, Denmark [DK], Liege, Belgium [BE] and Sheffield, United Kingdom [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 the concordance correlation coefficient for PINP 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. Results We showed that both EDTA plasma and serum were suitable for PINP determination. We observed a significant proportional bias between Orion radioimmunoassay and the automated methods for PINP (Roche Cobas and IDS iSYS), which both gave very similar results. The multivariate model did not improve the excellent correlation that was observed between the methods. Conclusions Harmonization of PINP assays is possible by applying a correction factor or correctly assigning the values of the calibrators. This work will benefit from further collaboration between assays manufacturers and clinical laboratory professionals.

Successful management of tertiary hyperparathyroidism associated with hypophosphataemic rickets in an adult.

Tertiary hyperparathyroidism (THP) is a rare complication in patients with hypophosphataemic rickets (HR), usually related to long-term management with active vitamin D analogues and oral phosphate salts. If left untreated, THP may aggravate bone and renal disease. We report a case of THP, which developed during the course of HR. Preoperatively, cinacalcet administration along with gradual increase in alphacalcidol dose, led to almost normalization of serum calcium and decrease in parathyroid hormone (PTH) concentrations. The patient underwent an uneventful subtotal parathyroidectomy, resulting in PTH normalization and stabilization of eucalcaemia during 18 months of follow-up. We conclude that, except for optimal dosage of elementary phosphate and alphacalcidol, cinacalcet prior to parathyroidectomy may be an effective option in patients with HR complicated with THP.

Autosomal Recessive Osteogenesis Imperfecta Caused by a Novel Homozygous COL1A2 Mutation.

Osteogenesis imperfecta (OI) is a skeletal dysplasia characterized by brittle bones and extraskeletal manifestations. The disease phenotype varies greatly. Most commonly, OI arises from monoallelic mutations in one of the two genes encoding type I collagen, COL1A1 and COL1A2 and is inherited as an autosomal dominant trait. Here, we describe a consanguineous family with autosomal recessive OI caused by a novel homozygous glycine substitution in COL1A2, NM_000089.3: c.604G>A, p.(Gly202Ser), detected by whole-genome sequencing. The index patient is a 31-year-old Greek woman with severe skeletal fragility. She had mild short stature, low bone mineral density of the lumbar spine and blue sclerae. She had sustained multiple long bone and vertebral fractures since childhood and had been treated with bisphosphonates for several years. She also had an affected sister with similar clinical manifestations. Interestingly, the parents and one sister, all carriers of the COL1A2 glycine mutation, did not have manifestations of OI. In summary, we report on autosomal recessive OI caused by a homozygous glycine-to-serine substitution in COL1A2, leading to severe skeletal fragility. The mutation carriers lacked OI manifestations. This family further expands the complex genetic spectrum of OI and underscores the importance of genetic evaluation for correct genetic counselling.

Physical activity may be a potent regulator of bone turnover biomarkers in healthy girls during preadolescence.

This study investigated the effects of different levels of habitual physical activity (PA) assessed by pedometry on bone turnover markers of preadolescent girls according to a cross-sectional experimental design. Sixty prepubertal girls of similar chronological age, bone age, maturity level, and nutritional status were assigned to a low PA (LPA; n = 25), a moderate PA (MPA; n = 17), or a high PA (HPA; n = 18) group. Dual-energy X-ray absorptiometry was used to measure areal bone mineral density (BMD) and bone mineral content (BMC) of the lumbar spine (L2-L4) and dominant hip (femoral neck and trochanter). Blood was collected for the measurement of alkaline phosphatase (ALP), bone-specific ALP (BSAP), procollagen type I N-terminal propeptide (PINP), C-terminal telopeptide of collagen I (CTX), parathyroid hormone (PTH), osteocalcin, thyroid-stimulating hormone, estradiol, testosterone, luteinizing hormone, and follicle-stimulating hormone concentrations. ANOVA revealed that the HPA group (18,695 ± 1244 steps per day) had a lower daily energy intake and body mass than the MPA group (10,774 ± 521 steps per day) and the LPA group (7633 ± 1099 steps per day). The HPA group had higher (P < 0.05) lumbar and hip BMD and hip BMC than the LPA group and higher (P < 0.05) lumbar BMD than the MPA group. The MPA group had higher (P < 0.05) hip BMC than the LPA group. The HPA group had greater (P < 0.05) values of BSAP, PINP, and ALP and lower (P < 0.05) values of PTH and CTX than the LPA group but not the MPA group. A partial correlation analysis (adjusted for body mass index) revealed a positive correlation of steps per day with BMD and BSAP concentration and a negative correlation with PTH and CTX concentration. In conclusion, PA increases BMD and BMC of premenarcheal girls by favoring bone formation over bone resorption.

Bone Quality Assessment as Measured by Trabecular Bone Score in Patients With End-Stage Renal Disease on Dialysis.

Patients with end-stage renal disease (ESRD) on maintenance hemodialysis (HD) exhibit osteoporosis and increased fracture risk. Dual-energy X-ray absorptiometry scan measurements and calculation of fracture risk assessment toll score underestimate fracture risk in these patients and do not estimate bone quality. Trabecular bone score (TBS) has been recently proposed as an indirect measure of bone microarchitecture. In this study, we investigated alterations of bone quality in patients with ESRD on HD, using TBS. Fifty patients with ESRD on HD, with a mean age 62 years, and 52 healthy individuals matched for age, body mass index, and gender, were enrolled. All participants had a bone mineral density (BMD) measurement by dual-energy X-ray absorptiometry scan at the lumbar spine, femoral neck, total hip, and 1/3 radius. TBS was evaluated using TBS iNsight. Serum fetuin-A and plasma fibroblast growth factor-23 (FGF-23) (C-terminal) were also measured. Patients on dialysis had significantly lower BMD values at all skeletal sites measured. Plasma FGF-23 levels significantly increased and serum fetuin-Α significantly decreased in patients on dialysis compared with controls. TBS was significantly reduced in patients on dialysis compared with controls (1.11 ± 0.16 vs 1.30 ± 0.13, p < 0.001, respectively) independently of age; BMD; duration of dialysis; and serum levels of alkaline phosphatase, 25-OH-vitamin D, parathyroid hormone, fetuin-A, or plasma FGF-23. Patients on HD who were diagnosed with an osteoporotic vertebral fracture had numerically lower TBS values, albeit without reaching statistical significance, compared with patients on dialysis without a fracture (1.044 ± 0.151 vs 1.124 ± 0.173, respectively, p = 0.079). Bone microarchitecture, as assessed by TBS, is significantly altered in ESRD on patients on HD independently of BMD values and metabolic changes that reflect chronic kidney disease-mineral and bone disorder.

Secondary aneurysmal bone cyst in McCune-Albright syndrome.

Polyostotic fibrous dysplasia in combination with caféau-lait macules and hyperfunctioning endocrinopathies consists of a rare clinical condition termed as McCune-Albright syndrome. Aneurysmal bone cysts are tumor-like cystic lesions, composed of blood-filled compartments. They may occur as primary lesions or secondary to other pathologies; most commonly giant cell tumors of bone. However, secondary aneurysmal bone cysts in McCune-Albright syndrome are exceptional. We present a 28-year-old female with McCune-Albright syndrome. She experienced precocious puberty at age 3 months. In childhood, she experienced multiple long bone fractures, facial deformity and progressive visual and hearing impairment. One year ago, she experienced a painful, gradually enlarging bone lesion involving the right ilium, pubic and ischial bone with groundglass appearance, septa, marginal sclerosis, endosteal scalloping and blow-out expansion resulting in localized thinning of the cortex. CT-guided needle biopsy of the pelvic lesion showed aneurysmal bone cyst. Selective arterial embolization was recommended, however, the patient and her relatives did not consent to proceed to treatment, and she remained in close surveillance thereafter.

Volumetric bone mineral density and bone geometry assessed by peripheral quantitative computed tomography in women with differentiated thyroid cancer under TSH suppression.

OBJECTIVE: TSH suppression therapy in patients with differentiated thyroid cancer (DTC) has been associated with adverse effects on areal bone mineral density (aBMD) only in postmenopausal women. The purpose of study was to examine the effect of TSH suppression therapy on skeletal integrity using peripheral quantitative computed tomography (pQCT) at the radius and tibia in pre- and postmenopausal women with DTC and controls. STUDY DESIGN AND PATIENTS: Subjects included 80 women with DTC (40 pre- and 40 postmenopausal) and 89 (29 and 60, respectively) controls. pQCT was performed at the radius and tibia, Dual-energy X-ray absorptiometry (DXA) at the hip and lumbar spine, while samples were taken for calciotropic hormones and bone markers. RESULTS: No differences were observed concerning aBMD by DXA. In premenopausal women, there were no significant differences concerning vBMD, while cortical thickness was higher at the radius in patients with DTC (P < 0·01) compared with controls. In postmenopausal women with DTC trabecular bone mineral content (BMC), area and vBMD were lower at the radius (all P < 0·05), while at the tibia trabecular BMC and vBMD were lower at the mixed transition zone (14% from the distal end, P < 0·05) compared with controls. Cortical thickness was lower at the radius (P < 0·01) in postmenopausal patients compared with controls. Serum CTX was higher in postmenopausal women with DCT (P < 0·01), while in premenopausal patients, parathyroid hormone (PTH) was lower (P = 0·01) compared with controls. CONCLUSIONS: TSH suppression therapy is associated with higher bone resorption only in postmenopausal women; this adversely affects trabecular and cortical bone properties especially at nonweight-bearing sites such as the radius.

Effects of teriparatide retreatment in a patient with ß-thalassemia major.

BACKGROUND: Bone disease is a frequent complication of ß-thalassemia major (ß-ΤΜ) and its etiology is multifactorial. Marrow expansion, chronic hypoxia, endocrine complications, and iron overload caused chiefly by chronic transfusion treatment are significant factors affecting skeletal health. Bone disease is prevalent even among patients on regular transfusions and adequate iron chelation. The life expectancy of patients with ß-thalassemia has increased during the past decade and so, nowadays, patients with thalassemia-associated bone disease (TBD) often require long-term management. There are limited data concerning their pharmacologic treatment. Bisphosphonates represent the most widely studied agents in such patients and there are no published studies about the effects of anabolic treatment. Retreatment with teriparatide has only occasionally been studied in patients with osteoporosis. CASE REPORT: We present a male adult patient with ß-ΤΜ with a history of low bone mass and multiple vertebral fractures, who required sequential treatment for his longstanding bone disease. He had exhibited considerable, albeit delayed, response to a course of teriparatide treatment for 18 months but subsequently, and while on alendronate, sustained an insufficiency fracture at the left ischiopubic ramus. A second trial of teriparatide treatment resulted in further remarkable increase in total hip and femoral neck bone mineral density. We present the patient's response to sequential treatment during an 8-year follow-up. CONCLUSION: Teriparatide could represent an alternative treatment for adults with TBD especially when long-term, sequential treatment is needed. Although there are limited data concerning retreatment, in selected cases, this might be considered.

Effect of parathyroidectomy versus risedronate on volumetric bone mineral density and bone geometry at the tibia in postmenopausal women with primary hyperparathyroidism.

The objective of the study was to evaluate the effect of parathyroidectomy (PTX) versus 35 mg once-weekly (ow) risedronate administration on volumetric bone mineral density (vBMD) and bone geometry at the tibia in postmenopausal women with primary hyperparathyroidism (PHPT). Our open-label prospective observational study included 32 postmenopausal women with PHPT as the study group: 16 underwent PTX and 16 were treated with 35 mg ow risedronate for 2 years. We assessed areal BMD (aBMD) by DXA, and vBMD and bone mineral content (BMC) (cortical and trabecular area) by peripheral quantitative computed tomography (pQCT) at the tibia at baseline and at 2 years. Risedronate did not result in any significant change on vBMD and structural pQCT indices. PTX resulted in significant increase in trabecular (trab) BMC (6.44 %) and vBMD (4.64 %), with percent increase being significantly higher than risedronate (p < 0.05). At cortical sites, there was no significant change following PTX. However, the percent change in cortical (cort) vBMD was higher following PTX versus risedronate (0.39 % vs. -0.26 %, p < 0.05). In conclusion, in postmenopausal women with PHPT, PTX is superior to ow risedronate, in terms of improvement of trabecular mineralization and vBMD at the tibia, whereas the effect at cortical sites is less pronounced.