Effects of anti-resorptive agents on trabecular bone score (TBS) in older women

Summary: We evaluated the longitudinal effects of anti-resorptive agents (534 treated women vs. 1,150 untreated) on lumbar spine bone mineral density (BMD) and trabecular bone score (TBS). TBS was responsive to treatment in women over age 50. The treatment-related increase in TBS was less than the increase in BMD, which is consistent with bone texture preservation. Introduction: In addition to inducing an increase in BMD, anti-resorptive agents also help to preserve bone architecture. TBS, a new gray-level texture measurement, correlates with 3D parameters of bone micro-architecture independent of BMD. Our objective was to evaluate the longitudinal effects of anti-resorptive agents on lumbar spine BMD and TBS. Methods: Women (≥50years), from the BMD program database for the province of Manitoba, Canada, who had not received any anti-resorptive drug prior to their initial dual X-ray absorptiometry (DXA) exam were divided into two groups: untreated, those without any anti-resorptive drug over the course of follow-up, and treated, those with a non-estrogen anti-resorptive drug (86% bisphosphonates, 10% raloxifene, and 4% calcitonin). Lumbar spine TBS was calculated for each lumbar spine DXA examination. Changes in TBS and BMD between baseline and follow-up (mean follow-up 3.7years), expressed in percentage per year, were compared between the two groups. Results: A total of 1,150 untreated women and 534 treated women met the inclusion criteria. Only a weak correlation was seen between BMD and TBS in either group. Significant intergroup differences in BMD change and TBS change were observed over the course of follow-up (p < 0.001). Similar mean decreases in BMD and TBS (−0.36%/year and −0.31%/year, respectively) were seen for untreated subjects (both p < 0.001). Conversely, treated subjects exhibited a significant mean increase in BMD (+1.86%/year, p < 0.002) and TBS (+0.20%/year, p < 0.001). Conclusion: TBS is responsive to treatment with non-estrogen anti-resorptive drug therapy in women over age 50. The treatment-related increase in TBS is less than the increase in BMD, which is consistent with bone texture preservatio

Hypercalcemia upon denosumab withdrawal in primary hyperparathyroidism: a case report and literature review.

Denosumab discontinuation is associated with a rapid increase in bone resorption and a decrease in bone mineral density. Spontaneous vertebral fractures may occur as a side effect of the rebound of bone resorption. Cases of rebound-linked hypercalcemia have also been described, moderate in women with osteoporosis and breast cancer and severe in children receiving oncological doses of denosumab. We report the case of an adult woman with primary hyperparathyroidism and moderate hypercalcemia, treated with denosumab for osteoporosis, who developed severe hypercalcemia and spontaneous vertebral fractures (SVFs) after denosumab discontinuation. An 86-year-old woman with densitometric osteoporosis was treated for 3 years with 60 mg of subcutaneous denosumab every 6 months. She was known to have primary hyperparathyroidism, with a serum albumin-corrected calcium of 2.82 mmol/l (NV 2.15-2.5) at the end of denosumab effect. Nine months after the last denosumab injection, she was hospitalized due to worsening overall health. Clinical evaluation revealed severe hypercalcemia (calcium 3.35 mmol/l). Very high values of bone turnover markers (BTMs) suggested a rebound effect due to denosumab discontinuation. An X-ray showed multiple new SVFs. After injection of denosumab 60 mg, serum calcium rapidly decreased and BTMs were dramatically reduced. A surgical approach by minimally invasive parathyroidectomy allowed for definite resolution of hyperparathyroidism and hypercalcemia. This case suggests that hypercalcemia can be a side consequence of denosumab discontinuation, which can become severe when other causes of hypercalcemia, such as primary hyperparathyroidism, are present

Risks and benefits of percutaneous vertebroplasty or kyphoplasty in the management of osteoporotic vertebral fractures

Vertebral fracture (VF) is the most common osteoporotic fracture and is associated with high morbidity and mortality. Conservative treatment combining antalgic agents and rest is usually recommended for symptomatic VFs. The aim of this paper is to review the randomized controlled trials comparing the efficacy and safety of percutaneous vertebroplasty (VP) and percutaneous balloon kyphoplasty (KP) versus conservative treatment. VP and KP procedures are associated with an acceptable general safety. Although the case series investigating VP/KP have all shown an outstanding analgesic benefit, randomized controlled studies are rare and have yielded contradictory results. In several of these studies, a short-term analgesic benefit was observed, except in the prospective randomized sham-controlled studies. A long-term analgesic and functional benefit has rarely been noted. Several recent studies have shown that both VP and KP are associated with an increased risk of new VFs. These fractures are mostly VFs adjacent to the procedure, and they occur within a shorter time period than VFs in other locations. The main risk factors include the number of preexisting VFs, the number of VPs/KPs performed, age, decreased bone mineral density, and intradiscal cement leakage. It is therefore important to involve the patients to whom VP/KP is being proposed in the decision-making process. It is also essential to rapidly initiate a specific osteoporosis therapy when a VF occurs (ideally a bone anabolic treatment) so as to reduce the risk of fracture. Randomized controlled studies are necessary in order to better define the profile of patients who likely benefit the most from VP/KP

Can one or two high doses of oral vitamin D3 correct insufficiency in a non-supplemented rheumatologic population?

Summary: We evaluated the effectiveness of supplementation with high dose of oral vitamin D3 to correct vitamin D insufficiency. We have shown that one or two oral bolus of 300,000IU of vitamin D3 can correct vitamin D insufficiency in 50% of patients and that the patients who benefited more from supplementation were those with the lowest baseline levels. Introduction: Adherence with daily oral supplements of vitamin D3 is suboptimal. We evaluated the effectiveness of a single high dose of oral vitamin D3 (300,000IU) to correct vitamin D insufficiency in a rheumatologic population. Methods: Over 1month, 292 patients had levels of 25-OH vitamin D determined. Results were classified as: deficiency 20ng/ml. The lowest the baseline value, the highest the change after 3months (negative relation with a correlation coefficient r = −0.3, p = 0.0007). Conclusions: We have shown that one or two oral bolus of 300,000IU of vitamin D3 can correct vitamin D insufficiency in 50% of patient

Osteogenesis imperfecta: from diagnosis and multidisciplinary treatment to future perspectives.

Osteogenesis imperfecta is an inherited connective tissue disorder with wide phenotypic and molecular heterogeneity. A common issue associated with the molecular abnormality is a disturbance in bone matrix synthesis and homeostasis inducing bone fragility. In very early life, this can lead to multiple fractures and progressive bone deformities, including long bone bowing and scoliosis. Multidisciplinary management improves quality of life for patients with osteogenesis imperfecta. It consists of physical therapy, medical treatment and orthopaedic surgery as necessary. Medical treatment consists of bone-remodelling drug therapy. Bisphosphonates are widely used in the treatment of moderate to severe osteogenesis imperfecta, from infancy to adulthood. Other more recent drug therapies include teriparatide and denosumab. All these therapies target the symptoms and have effects on the mechanical properties of bone due to modification of bone remodelling, therefore influencing skeletal outcome and orthopaedic surgery. Innovative therapies, such as progenitor and mesenchymal stem cell transplantation, targeting the specific altered pathway rather than the symptoms, are in the process of development

A single high dose of oral vitamin D3 is insufficient to correct a deficiency in a rheumatologic population

Introduction Vitamin D plays a major role in bone metabolismand neuromuscular function. Supplementation with vitamin D iseffective to reduce the risk of fall and of fracture. However adherenceto oral daily vitamin D is low. Screening and correcting vitamin Dinsufficiency in a rheumatologic population could improve bothmorbidity and quality of life. After determining the prevalence ofvitamin D deficiency in this population, we evaluated if supplementationwith a single high dose of oral 25-OH vitamin D3 wassufficient to correct this abnormality.Methods During one month (November 2009), levels of 25-OHvitamin D were systematically determined in our rheumatology outpatientclinic and classified in: vitamin D deficiency (&lt; 10 μg/l),vitamin D insufficiency (10 to 30 μg/l) or normal vitamin D (&gt; 30 μg/l).Patients with insufficiency or deficiency received respectively a singlehigh dose of 300'000 IU or 600'000 IU oral vitamin D3. In addition,all patients with osteoporosis were prescribed daily supplement ofcalcium (1 g) and vitamin D (800 IU). 25-OH vitamin D levels werereevaluated after 3 months.Results Vitamin D levels were initially determined in 292 patients(mean age 53, 211 women, 87 % Caucasian). 77 % had inflammatoryrheumatologic disease (IRD), 20 % osteoporosis (OP) and 12 %degenerative disease (DD). Vitamin D deficiency was present in 20(6.8 %), while 225 (77.1 %) had insufficiency. Of the 245 patientswith levels &lt; 30μg/l, a new determination of vitamin D level wasavailable in 173 (71 %) at 3 months.Conclusion Vitamin D insufficiency is highly prevalent in ourrheumatologic population (84 %), and is not adequately correctedby a single high dose of oral vitamin D3 in &gt; 50 % of the patientswith IRD and DD. In patients with OP, despite association of asingle high dose with daily oral vitamin D supplementation, 40 %of patients are still deficient when reevaluated at 3 months

High prevalence of hypovitaminosis D in a Swiss rheumatology outpatient population.

Vitamin D is important for bone metabolism and neuromuscular function. While a routine dosage is often proposed in osteoporotic patients, it is not so evident in rheumatology outpatients where it has been shown that the prevalence of hypovitaminosis D is high. The aim of the current study was to systematically evaluate the vitamin D status in our outpatient rheumatology population to define the severity of the problem according to rheumatologic diseases. During November 2009, all patients were offered a screening test for 25-OH vitamin D levels and categorised as deficient (&lt;10 µg/l [ng/ml] [25 nmol/l]), insufficient (10 µg/l to 30 µg/l [25 to 75 nmol/l]) or normal (&gt;30 µg/l [75 nmol/l]). A total of 272 patients were included. The mean 25-OH vitamin D level was 21 µg/l (range 1.5 to 45.9). A total of 20 patients had vitamin D deficiency, 215 patients had an insufficiency and 37 patients had normal results. In the group of patients with osteoporosis mean level of 25-OH vitamin D was 25 µg/l and 31% had normal results. In patients with inflammatory rheumatic diseases (N = 219), the mean level of 25-OH vitamin D was 20.5 µg/l, and only 12% had normal 25-OH vitamin D levels. In the small group of patients with degenerative disease (N = 33), the mean level of 25-OH vitamin D was 21.8 µg/l, and 21% had normal results. Insufficiency and deficiency were even seen in 38% of the patients who were taking supplements. These results confirm that hypovitaminosis D is highly prevalent in an outpatient population of rheumatology patients, affecting 86% of subjects. Despite oral supplementation (taken in 38% of our population), only a quarter of those on oral supplementation attained normal values of 25-OH vitamin D

Are patients with hypermobile Ehlers-Danlos syndrome or hypermobility spectrum disorder so different?

Diagnosing hypermobile Ehlers-Danlos syndrome (hEDS) remains challenging, despite new 2017 criteria. Patients not fulfilling these criteria are considered to have hypermobile spectrum disorder (HSD). Our first aim was to evaluate whether patients hEDS were more severely affected and had higher prevalence of extra-articular manifestations than HSD. Second aim was to compare their outcome after coordinated physical therapy. Patients fulfilling hEDS/HSD criteria were included in this real-life prospective cohort (November 2017/April 2019). They completed a 16-item Clinical Severity Score (CSS-16). We recorded bone involvement, neuropathic pain (DN4) and symptoms of mast cell disorders (MCAS) as extra-articular manifestations. After a standardized initial evaluation (T0), all patients were offered the same coordinated physical therapy, were followed-up at 6 months (T1) and at least 1 year later (T2), and were asked whether or not their condition had subjectively improved at T2. We included 97 patients (61 hEDS, 36 HSD). Median age was 40 (range 18-73); 92.7% were females. Three items from CSS-16 (pain, motricity problems, and bleeding) were significantly more severe with hEDS than HSD. Bone fragility, neuropathic pain and MCAS were equally prevalent. At T2 (20 months [range 18-26]) 54% of patients reported improvement (no difference between groups). On multivariable analysis, only family history of hypermobility predicted (favorable) outcome (p = 0.01). hEDS and HDS patients showed similar disease severity score except for pain, motricity problems and bleeding, and similar spectrum of extra-articular manifestations. Long-term improvement was observed in &gt; 50% of patients in both groups. These results add weight to a clinical pragmatic proposition to consider hEDS/HSD as a single entity that requires the same treatments

Impact of a fracture liaison service on patient management after an osteoporotic fracture: the CHUV FLS.

In 2008, the Centre Hospitalier Universitaire Vaudois (CHUV, Lausanne, Switzerland) initiated a Fracture Liaison Service (FLS). All patients hospitalised for a low trauma fracture are identified by the FLS. Inpatients then choose to be managed by either the FLS team or their general practitioner (GP). In this study we compared the management between the FLS team and the GP in terms of diagnosis of osteoporosis, treatment, refracture rates and mortality after FLS recording. Results are compared with the management of osteoporosis before the creation of the FLS, as reported in the survey study Osteocare. A total of 606 patients were included (80% women); 55% chose management by the FLS and 45% their GP. The mean age was 78.5, and hip was the main fracture site (44%). The percentage of patients having dual X-ray absorptiometry to diagnose osteoporosis was significantly higher in the FLS group than the GP group (72 vs 26.5%, p &lt;0.01). This percentage was 31.4% in the Osteocare study. Overall, 50.3% of patients in the FLS group had osteoporosis versus 57.5% in the GP group (p &lt;0.05). This percentage was 46.0% in the Osteocare study. Use of osteoporosis medication was higher in the FLS group (FLS 100% of the patients, GP 44.1%, p &lt;0.001) and had increased since the Osteocare study (21.6%). One-year nonvertebral refracture rate was higher in GP group than in the FLS patients (5.1 vs 3.0%, p &lt;0.05), whereas more vertebral fractures were identified in the FLS group, owing to protocol-driven regular clinical and vertebral fracture assessment (VFA) evaluations (number of evaluations 8 vs 0, p &lt;0.01). Unadjusted mortality was higher in GP group than in the FLS group at one and five years (6.93 vs 2.11% and 33.58 vs. 15.96%, p &lt;0.04). After adjustment by age and fracture site, these results were not significant. With FLS management, diagnosis and treatment of osteoporosis were more frequent than with GP management; new nonvertebral fractures were less frequent. Moreover, both forms of management had increased relative to rates reported in a 2004-2006 nationwide survey Osteocare, before FLS creation