Severe Postmenopausal Osteoporosis Research Articles

Τhe story of sclerostin inhibition: the past, the present, and the future.

Sclerostin inhibits osteoblast activity by hampering activation of the canonical Wnt signaling pathway and simultaneously stimulates osteoclastogenesis through upregulation of the receptor activator of NFκB ligand (RANKL). Thus, antibodies against sclerostin (Scl-Abs), besides promoting bone formation, suppress bone resorption and dissociate bone formation from resorption. This dual action results in remarkable increases of bone mineral density which are of a greater magnitude compared to the other antiosteoporotic treatments and are accompanied by decreases of fracture risk at all skeletal sites. The anabolic effect subsides after the first few months of treatment and a predominantly antiresorptive effect remains after this period, limiting its use to 12months. Furthermore, these effects are largely reversible upon discontinuation; therefore, subsequent treatment with antiresorptives is indicated to maintain or further increase the bone gains achieved. Romosozumab is currently the only Scl-Ab approved for the treatment of severe postmenopausal osteoporosis. Indications for use in other populations, such as males, premenopausal women, and patients with glucocorticoid-induced osteoporosis, are pending. Additionally, the efficacy of Scl-Abs in other bone diseases, such as osteogenesis imperfecta, hypophosphatasia, X-linked hypophosphatemia, and bone loss associated with malignancies, is under thorough investigation. Cardiovascular safety concerns currently exclude patients at high cardiovascular risk from this treatment.

Verification of efficacy and safety of ibandronate or denosumab for postmenopausal osteoporosis after 12-month treatment with romosozumab as sequential therapy: The prospective VICTOR study.

Romosozumab is a potent drug for treating postmenopausal osteoporosis but has a limited dosing period of 12months. Bone mineral density (BMD) decreases soon after romosozumab discontinuation, thus emphasizing the importance of appropriate sequential treatment. The present VICTOR randomized controlled study compared the efficacy of ibandronate and denosumab as sequential therapy options following 12-month romosozumab treatment. Subjects completing 12months of romosozumab administration for severe postmenopausal osteoporosis were randomly assigned to receive either ibandronate or denosumab for an additional 12months. The primary outcome of interest was the percentage changes in BMD at the lumbar spine, total hip, and femoral neck from 12months (completion of romosozumab) to 18 and 24months of total treatment (6 and 12months, respectively, after the conversion to sequential therapy). Secondary outcomes included alterations in serum bone turnover markers and the incidence of adverse events. Sixty-two subjects each in the ibandronate and denosumab groups completed the sequential therapy. The respective percentage changes in BMD at the lumbar spine from 12months to 24months were 2.5% in the ibandronate group and 5.4% in the denosumab group. At 24months, we observed significant differences versus 12months for both groups as well as between the groups (all P<0.01), showing a superior ability to increase BMD at the lumbar spine for denosumab over ibandronate. BMD gains at the total hip and femoral neck exhibited comparably favorable trends. P1NP and TRACP-5b were significantly decreased from 12 to 24months (-64.9% and-26.8% in the ibandronate group and-67.4% and-36.3% in the denosumab group, respectively; all P<0.001 versus 12months). Several minor adverse events were recorded in both groups, none of which led to the discontinuation of the trial. The VICTOR study revealed that denosumab could be considered more effective than ibandronate, with few severe adverse events, for the enhancement of BMD as a sequential agent after romosozumab in postmenopausal osteoporosis patients.

Switching to Denosumab or Bisphosphonates After Completion of Teriparatide Treatment in Women With Severe Postmenopausal Osteoporosis

ObjectiveTo compare bone mineral density (BMD) changes after 12 months of treatment with denosumab or bisphosphonates in postmenopausal women with severe osteoporosis after stopping teriparatide therapy. MethodsWe retrospectively analyzed 140 postmenopausal women (mean age, 74.2 years) with severe osteoporosis who had been treated with teriparatide for 18 to 24 months at our outpatient clinic in a tertiary endocrine center between 2006 and 2015. After stopping teriparatide therapy, they continued treatment with a bisphosphonate (alendronate, risedronate, ibandronate, or zoledronic acid) or denosumab while receiving daily vitamin D and calcium. BMD at the lumbar spine (LS), total hip (TH), and femoral neck (FN) was measured by dual energy x-ray absorptiometry when teriparatide therapy was discontinued (baseline) and after 12 months of further treatment. Multivariate linear regression models were used to identify the predictors of BMD gain. ResultsAfter stopping teriparatide therapy, 70 women continued treatment with bisphosphonates and 70 received denosumab. LS, but not TH or FN, BMD gain was significantly greater in the denosumab group than in the bisphosphonates group at 12 months. Multivariate analysis showed that BMD gain at the LS was negatively associated with bisphosphonate versus denosumab treatment and positively associated with baseline serum total procollagen type I N-terminal propeptide. BMD gains at the FN were predicted by higher baseline serum urate levels. BMD gains at the TH and FN were negatively associated with pretreatment BMD gains at the same site. ConclusionTwelve months after stopping teriparatide therapy, sequential denosumab treatment appeared to yield higher additional LS BMD gain on average compared with bisphosphonates treatment.

Cost effectiveness of romosozumab versus teriparatide for severe postmenopausal osteoporosis in Japan.

This study aims to assess the cost effectiveness of romosozumab versus teriparatide, both sequenced to alendronate, for the treatment of severe postmenopausal osteoporosis in Japanese women previously treated with bisphosphonates. A Markov model was used to assess the relative cost effectiveness of 1 year of romosozumab versus 2 years of teriparatide, both sequenced to alendronate for a total treatment duration of 5 years. Outcomes for a cohort of women with a mean age of 78 years, a T-score ≤-2.5 and a previous fragility fracture were simulated over a lifetime horizon. The analysis was conducted from the perspective of the Japanese healthcare system and used a discount rate of 2% per annum. To inform relative fracture incidence, the bone mineral density (BMD) advantage of romosozumab over teriparatide was translated into relative risks of fracture, using relationships provided by a meta-regression of osteoporosis therapy trials. Outcomes were assessed in terms of lifetime costs (2020 US dollars) and quality-adjusted life years (QALYs). Base case results showed that, compared with teriparatide/alendronate, romosozumab/alendronate reduced costs by $5134 per patient and yielded 0.045 additional QALYs. Scenario analyses and probabilistic sensitivity analysis confirmed that results are robust to uncertainty in model assumptions and inputs. Results show that romosozumab/alendronate produces greater health benefits at a lower total cost than teriparatide/alendronate.

Restoration of the intravertebral stability in Kümmell's disease following the treatment of severe postmenopausal osteoporosis by 1-34PTH-a retrospective study.

Kümmell's disease (KD) patients with severe osteoporosis were applied by the 1-34PTH; the fracture union and the increased bone mineral density (BMD) following this treatment were retrospectively reviewed. Twenty-one postmenopausal osteoporosis (PMOP) patients with KD received at least 6 months of 1-34PTH treatment. The medical records, including clinical evaluation symptoms, radiological evaluation for bone union and the stability of intravertebral vacuum cleft (IVC), BMD, and laboratory examination for osteoporosis recovery and health-related quality of life (HRQOL), were reviewed. From baseline to month 12, visual analog scale decreased from 8.24 ± 0.54 to 1.71 ± 0.56 (P < 0.001) and the modified Japanese Orthopedic Association scores increased from 6.86 ± 1.77 to 10.43 ± 1.29 (P < 0.001). Sagittal CT demonstrated that the IVC was filled or bridged by the osseous tissue in all patients. Within the vertebra, the IVC area (IVCA) decreased from 4.50 ± 2.50 to 0 mm2 (P = 0.001) and the mineralized bone area (MBA) increased from 170.91 ± 102.23 to 259.56 ± 98.60 mm2 (P < 0.001). The area ratio of IVC to vertebra decreased from 0.97 ± 0.46 to 0% (P < 0.001), and the area ratio of mineral bone to vertebra was increased from 32.85 ± 14.51 to 54.97 ± 14.01% (P < 0.001). The kyphosis angle increment was 3.43 ± 1.80°, and the loss rate of anterior border height was 11.14 ± 4.82%. No differences were found in posterior border height and spinal canal diameter. The PINP, β-CTx, BMD, and Short Form-36 Health Survey scores markedly increased. In KD patients with severe PMOP, 1-34PTH treatment could alleviate the clinical evaluation symptoms, facilitate the recovery of the intravertebral stability, ameliorate the BMD, and improve the HRQoL.

Romosozumab: a Review of Efficacy, Safety, and Cardiovascular Risk.

Authors review the safety and efficacy of romosozumab for the treatment of osteoporosis as demonstrated in three phase III clinical trials and offer insights into the potential cardiovascular risk associated with its use. Incidence of new vertebral fracture is dramatically reduced with 12months of romosozumab use in comparison to both placebo and active bisphosphonate control groups in patients with postmenopausal osteoporosis. Significant non-vertebral anti-fracture benefit was also demonstrated in patients with more severe osteoporosis. Numerical increases in cardiovascular events call into question the safety of romosozumab use, particularly in patients with cardiovascular history or at high cardiovascular risk. Romosozumab has impressive anti-fracture effects in postmenopausal women with high risk for fragility fracture. Despite no significant differences in baseline cardiovascular risk factors between groups, a numerical increase in serious cardiovascular adverse events was demonstrated with romosozumab in randomized trials with no discernable etiology. Until more real-world evidence is available, romosozumab should not be used in patients with a recent cardiovascular event and should be used cautiously in patients with high cardiovascular risk. Romosozumab's place in therapy is likely patients with severe postmenopausal osteoporosis and low cardiovascular risk.

Outcomes of Treatment in Patients with Severe Postmenopausal Osteoporosis: The Effects of Teriparatide Treatment on Bone Mineral Density, Back Pain and Biochemical Parameters

Outcomes of Treatment in Patients with Severe Postmenopausal Osteoporosis: The Effects of Teriparatide Treatment on Bone Mineral Density, Back Pain and Biochemical Parameters

A case of atypical femur fracture during long-term treatment with bisphosphonates in patient with postmenopausal osteoporosis

Bisphosphonates is a first-line therapy for treatment of osteoporosis. In the last decade, the number of atypical femur fracture (AFF) cases during long-term treatment with bisphosphonates has increased. The aim of this article was to analyze the literature data on this problem, to define the diagnostic criteria of AFF and to present the case of AFF in the patient who received treatment with alendronate for 3.5 years.&#x0D; A 78-year-old woman, receiving oral bisphosphonate for severe postmenopausal osteoporosis for 3.5 years, suddenly started feeling pain in her right thigh while walking. Three months later, she had got a fracture in middle third of the right femur after falling from her standing height. According to instrumental diagnostics, this fracture had all criteria of AFF. Blocking intramedullary osteosynthesis with shafts was performed. A retrospective analysis of soft tissue magnetic resonance imaging in the area of right thigh, done before the fracture, showed the presence of undiagnosed incomplete right femur fracture in the middle third, which subsequently led to a complete fracture.&#x0D; Presented clinical case demonstrates the complexity of AFF diagnostics. The purpose of the publication is to draw attention of medical specialists to the issue of this rare side effect of bisphosphonate treatment.

Влияние на бюджет системы здравоохранения применения препарата терипаратид при лечении пациентов с тяжелым остеопорозом в сравнении с антирезорбитивными препарами

Objective: budget impact assessment on the healthcare system use of teriparatide in the treatment of severe osteoporosis in comparison with antiresorptive drugs. Material and methods. Study Design – retrospective literature analysis. Methods of pharmacoeconomic analysis: cost analysis, the “budget impact” analysis, sensitivity analysis. In the study, patients were considered as a target group for prescribing the drug teriparatide or antiresorptive therapy with severe postmenopausal osteoporosis with the presumed development of two compression fractures requiring surgical reconstruction. Results. The use of teriparatide in patients with two low-traumatic vertebral fractures will require a cost 1.4% less than treatment with zoledronic acid and 33.07% less than the treatment with alendronic acid and 13.6% less in comparison with the use of denosumab. At a weighted average frequency of 3 clinically significant fractures per year, the use of teriparatide will require 15.0%, 42.9% and 24.7% less cost, respectively. For a group of 1000 patients with 2 fractures per year, the savings over 4 years will amount to 13.7 million rubles, 483.0 million rubles, respectively and 154.1 million rubles. With a more severe course, expressed in an increase in the number of fractures to 3 per year, budget savings over 4 years per 1000 patients will amount to 219.0 million rubles, 930.9 million rubles and 406.0 million rubles, respectively. A sensitivity analysis showed that on a 4-year horizon, the use of teriparatide remains economically feasible with a decrease in the frequency of fractures to 1.95 per year compared to zoledronic acid, to 1.4 per year compared to denosumab and to 0.95 per year compared alendronic acid. Conclusion. Teriparatide is more cost effective than antiresorptive drugs for severe osteoporosis, when an average of 2 clinically significant vertebral fractures per year can be expected in untreated patients requiring surgical reconstruction. In this way, the appointment of teriparatide as the first line of therapy for osteoporosis in patients at high risk of fractures, having more than one clinically significant fracture of the vertebral body in a history is justified from a pharmacoeconomic point of view.

Teriparatide in the Treatment of Severe Postmenopausal Osteoporosis: A Cost-Utility Analysis.

Teriparatide is a new agent serves as a treatment of choice for severe post-menopausal osteoporotic patients who are at high risk of fracture or have failed or been intolerant of previous osteoporosis therapy. The objective of this study is to estimate the cost-utility of teriparatide compared with no treatment from health system perspective in Iran. A micro-simulation model was developed for a cohort of hypothetical Iranian patient population (women aged 70 years, T-score -2.5 with previous fracture or T-score -3.0 without prior fracture) over a lifetime horizon. The model consisted of the seven health states. During each cycle, patients could have a fracture, remain healthy, remain in a post-fracture state or die. Background fracture risks, mortality rates, persistence rates, utilities, medical and drug costs were derived using published sources. Total accumulated life-time costs and quality-adjusted life years (QALYs) were estimated. Teriparatide was associated with 4.786 QALYs and total direct costs of IRR 143,168,259 over a lifetime horizon. Compared to no treatment, teriparatide provided an additional 0.145 QALY at an incremental cost of IRR 33,511,013. The resulting incremental cost-effectiveness ratio was IRR 230,333,030/QALYs gained. The probabilistic analysis showed that accepting a willingness-to-pay 2 and 3 GDP/capita in Iran, the probability of teriparatide being cost-effective were 51% and 83%, respectively. Compared to no treatment, teriparatide was indicated to be more costly and associated with fewer fractures, more life-years, and more QALYs. The result showed that teriparatide may be considered a cost-effective intervention when targeted to the appropriate patients.

Skeletal response to treatment with teriparatide (TPD) after bisphosphonate in post-menopausal women with osteoporosis and a high prevalence of secondary risk factors in real-life setting of a metabolic bone clinic; effect of age and vitamin D status

ABSTRACTPurpose: Teriparatide (TPD) is a skeletal anabolic agent used in patients with severe post-menopausal osteoporosis (PMO) and steroid-induced osteoporosis who are at hish risk of fracture. Predictors of therapeutic response to teriparatide in real-life setting are not well characterised. We investigated potential factors associated with teriparatide response in post-menopausal women with established osteoporosis.Methods: We carried out a retrospective survey of 48 women, aged 73.2 [7.5] years with severe osteoporosis and prevalent fractures treated with TPD according to the NICE criteria. BMD was measured at baseline, 6-12 and 18-24 months at the lumbar spine (LS), total hip (TH) and femoral neck (FN). Bone turnover markers, serum 25 (OH)vitamin D were determined at 3-12 and 12-24 months.Results: BMD increased at 6-12 months (% change mean [SEM] 6.5 [1.1] p = 0.004) and 18-24 months (8.45 % [1.2] p<0.001) at the LS. A significant increase in BMD was observed at FN (3.1 [1.3] % p = 0.02). Changes in BMD at the TH was higher in patients younger than 73 years compared to older women (% change in BMD 4.13 [1.64] % v/s -1.7 [1.1] p = 0.007). Baseline 25 (OH) vitamin D correlated with change in P1NP at 3-12 months (r = 0.45 p = 0.049).Conclusions: TPD-induced changes in BMD at the TH appears may be dependent on age. Vitamin D status may influence the early anabolic effect to TPD. Our data suggest that these factors may be important considerations when initiating and optimising treatment with TPD, although further larger studies are needed to confirm these findings.

The effect of denosumab or bisphosphonates in women with severe postmenopausal osteoporosis after completion of teriparatide treatment

The effect of denosumab or bisphosphonates in women with severe postmenopausal osteoporosis after completion of teriparatide treatment

Teriparatide and denosumab combination therapy and skeletal metabolism.

Fifty-nine women over 65years old with severe postmenopausal osteoporosis (evidence of at least two moderate-severe vertebral fractures) were enrolled in the study. Serum samples were collected every 3months. They were assayed for intact N-propeptide of type I collagen (P1NP), C-terminal telopeptide of type I collagen (CTX), intact parathyroid hormone (PTH), 25 hydroxy-vitamin D (25 OHD), Sclerostin (SOST), and Dickkopf-related protein 1 (DKK1). Bone mass density was assessed by dual-energy X-ray absorptiometry at the lumbar spine and at the total hip. In the groups treated only with TPTD or with denosumab, bone turnover markers increased and decreased, respectively. In TPTD group, a later significant increase in DKK1 was observed, while in denosumab group, a progressive increase in SOST was associated with a progressive significant decrease in DKK1. In the group treated first with denosumab and in which TPTD was added 3months later, both CTX and P1NP increased 3months after the beginning of TPTD. The strong effect of denosumab on bone turnover seems to be reversed by TPTD treatment. In this study, we showed that TPTD is able to express its biological activity even when bone turnover is fully suppressed by denosumab treatment. The combination therapy is associated with significant increases in both DKK1 and SOST.

Teriparatide (rhPTH1-34) Anabolic Therapy for Treatment of Type II Dens Fracture Non-union in Elderly Patients: Report of 5 Cases

Introduction Type II dens fracture is the most common cervical spine fracture type in elderly patients. Treatment options for this common injury include conservative management (i.e., hard collar or Halo Vest immobilization) or surgery. Delayed union or non-union is a frequent complication in elderly patients and is associated with an increased morbidity and mortality due to prolonged immobilization and hospitalization. The rhPTH1–34 (Teriparatide) is the recombinant form of the biologically active component of the human parathyroid hormone, currently approved for treatment of severe post-menopausal osteoporosis. However many in vitro studies have also demonstrated the efficacy of rhPTH1–34 in stimulating osteogenesis and bone healing and a few case reports have been published on its use in humans for treatment of fracture non-unions. The aim of this study is to report our successful experience with the use of rhPTH1–34 in the treatment of 5 cases of dens fracture non-union in elderly patients. Material and Methods Five patients (age &gt; 70, all females) diagnosed with type II C2 dens fracture non-union (no neurological compromise) were enrolled in this study. Fracture non-union was defined as non- healing at 9 months after injury and radiographic evidence of failed healing progression over the last 3 months. All patients had been treated conservatively with a hard collar. Patients were started on anabolic drug therapy with daily subcutaneous injection of rhPTH1–34 (Teriparatide, 20 ng/die) for 3 months. Regular clinical assessments and monitoring of serum levels of calcium, phosphorus, vitamin D, and alkaline phosphatase were undertaken throughout the treatment period. We describe the evolution of our cases over time with serial CT scan imaging as well as HRQoL questionnaires (VAS, SF-12, and Eq. 5D). Results Successful complete fracture healing was achieved in all patients at 74.5 ± 4.4 weeks after the injury and at 10.2 ± 3.8 weeks after the start of the anabolic therapy. Mean VAS score at the end of the treatment was 2.4 ± 1.3 (from a baseline value of 6.8 ± 2, p &lt; 0.02) in all patients, while the average SF-12 score was 42 ± 3.7 (PCS) and 61.5 ± 2.11 (MCS) (from a baseline value of 25.1 ± 2.12 and 43.2 ± 1.49, p &lt; 0.04) and Eq. 5D was 0.798 ± 0.044 (from a baseline value of 0.396 ± 0.198, p &lt; 0.03). Patients had normal serum calcium level (9.1 ± 0.9 mg/dl). No side effects related to the use of the anabolic therapy were noted in our patients. Conclusion Our case series shows that rhPTH1–34 has induced successful bone healing in all our cases of type II dens fracture non-union. Bone healing has been demonstrated through CT imaging and also confirmed by clinical improvement of HRQoL measures. This is a potentially groundbreaking finding in management of elderly patients with upper cervical injuries and will deserve further study in future.

Serum chitotriosidase in postmenopausal women with severe osteoporosis.

Human chitotriosidase (Chit) increases during the osteoclast differentiation and their activity. We demonstrated that serumChit was significantly higher in osteoporotic subjects than in healthy control ones and revealed a negative correlation between Chit and bone mineral density (BMD). This is the first study showing a correlation between Chit and severe postmenopausal osteoporosis. Mammalian chitinases exert important biological roles in the monocyte lineage and chronic inflammatory diseases. In particular, Chit seems to promote bone resorption in vitro. No in vivo studies have been performed to confirm this finding. We aim to evaluate Chit activity in postmenopausal women affected by severe osteoporosis. In this cross-sectional study, 91 postmenopausal women affected by osteoporosis and 61 with either osteopenia or normal BMD were screened. All subjects were assessed by dual-energy X-ray absorptiometry (DXA) and X-ray vertebral morphometry. Osteoporotic subjects were considered eligible if they were affected by at least one vertebral osteoporotic fracture (group A = 57 subjects). Osteopenic or healthy subjects were free from osteoporotic fractures (group B = 51 subjects). Enzymatic Chit and serum β-CrossLaps (CTX) were measured in the whole population. Group A showed higher serum levels of beta-CTX compared to group B (0.40 ± 0.26ng/mL vs 0.29 ± 0.2ng/mL, p = 0.022). Chit was significantly higher in group A than in group B (1042 ± 613nmol/mL/h vs 472 ± 313nmol/mL/h, p < 0.001, respectively) even after adjustment for age (p < 0.001). Spearman correlation test revealed a negative correlation between Chit and BMD at each site (lumbar spine: r = -0.38, p = 0.001, femoral neck: r = -0.35, p = 0.001, total femur: r = -0.39, p < 0.001). Furthermore, a positive correlation between Chit and PTH was observed (r = 0.26, p = 0.013). No significant correlation was found between Chit and beta-CTX (r = 0.12, p = 0.229). After a multivariate analysis, a positive correlation between severe osteoporosis and Chit (p < 0.001), beta-CTX (p = 0.013), and age (p < 0.001) was observed. This is the first clinical study showing a correlation between Chit and severe postmenopausal osteoporosis. Larger and prospective studies are needed to evaluate if Chit may be a promising clinical biomarker and/or therapeutic monitor in subjects with osteoporosis.

Efficacy of Denosumab on bone metabolism after a 12-month treatment, in women with severe post-menopausal osteoporosis

Efficacy of Denosumab on bone metabolism after a 12-month treatment, in women with severe post-menopausal osteoporosis

Comparison of efficacy teriparatide between denosumab and on hip BMD in women with severe post-menopausal osteoporosis

Comparison of efficacy teriparatide between denosumab and on hip BMD in women with severe post-menopausal osteoporosis

Effective osteoporosis treatment with teriparatide is associated with enhanced quality of life in postmenopausal women with osteoporosis: the European Forsteo Observational Study

BackgroundTo describe changes in health-related quality of life (HRQoL) of postmenopausal women with osteoporosis treated with teriparatide for up to 18 months and followed-up for a further 18 months, and to assess the influence of recent prior and incident fractures.MethodsThe European Forsteo Observational Study (EFOS) is an observational, prospective, multinational study measuring HRQoL using the EQ-5D. The primary objective was to assess changes in HRQoL during 36 months in the whole study population. A secondary post-hoc analysis examined fracture impact on HRQoL in four subgroups classified based on recent prior fracture 12 months before baseline and incident clinical fractures during the study. Changes from baseline were analysed using a repeated measures model.ResultsOf the 1581 patients, 48.4% had a recent prior fracture and 15.6% of these patients had an incident fracture during follow-up. 10.9% of the 816 patients with no recent prior fracture had an incident fracture. Baseline mean EQ-VAS scores were similar across the subgroups. In the total study cohort (n = 1581), HRQoL (EQ-VAS and EQ-5D index scores) improved significantly from baseline to 18 months and this improvement was maintained over the 18-month post-teriparatide period. Improvements were seen across all five EQ-5D domains during teriparatide treatment that were maintained after teriparatide was discontinued. Subjects with incident clinical fractures had significantly less improvement in EQ-VAS than those without incident fractures. Recent prior fracture did not influence the change in EQ-VAS during treatment.ConclusionsEFOS is the first longitudinal study in women with severe postmenopausal osteoporosis in the real world setting to show a substantial improvement in HRQoL during teriparatide treatment that was sustained during subsequent treatment with other medications. The increase in HRQoL was lower in the subgroups with incident fracture but was not influenced by recent prior fracture. The results should be interpreted in the context of the design of an observational study.

Association Between Polymorphisms of VDR, COL1A1, and LCT Genes and Bone Mineral Density in Belarusian Women With Severe Postmenopausal Osteoporosis

BACKGROUND AND OBJECTIVE. Variation of osteoporosis in the population is the result of an interaction between the genotype and the environment, and the genetic causes of osteoporosis are being widely investigated. The aim of this study was to analyze the association between the polymorphisms of the vitamin D receptor (VDR), type I collagen (COL1A1), and lactase (LCT) genes and severe postmenopausal osteoporosis as well as bone mineral density (BMD). MATERIAL AND METHODS. A total of 54 women with severe postmenopausal osteoporosis and 77 controls (mean age, 58.3 years [SD, 6.2] and 56.7 years [SD, 7.42], respectively) were included into the study. The subjects were recruited at the City Center for Osteoporosis Prevention (Minsk, Belarus). Dual-energy x-ray absorptiometry was used to measure bone mineral density at the lumbar spine and the femoral neck. Severe osteoporosis was diagnosed in the women with the clinical diagnosis of postmenopausal osteoporosis and at least 1 fragility fracture. The control group included women without osteoporosis. Polymorphic sites in osteoporosis predisposition genes (ApaI, BsmI, TaqI, and Cdx2 of the VDR gene, G2046T of the COL1A1 gene, and T-13910C of the LCT gene) were determined using the polymerase chain reaction on the deoxyribonucleic acid isolated from dried bloodspots. RESULTS. The data showed that the ApaI and BsmI polymorphisms of the VDR gene and T- 13910C of the LCT gene were associated with severe postmenopausal osteoporosis in the analyzed Belarusian women (P<0.01). A statistically significant positive correlation between the VDR risk genotypes ApaI and TaqI and bone mineral density was found (P<0.05). CONCLUSIONS. The findings of this study suggest that at least the ApaI and BsmI polymorphisms of the VDR gene and T-13910C of the LCT gene are associated with the risk of postmenopausal osteoporosis in our sample of the Belarusian women.

Evaluation of persistence and adherence to teriparatide treatment in patients affected by severe osteoporosis (PATT): a multicenter observational real life study

Osteoporosis is a chronic condition leading to an increased risk of developing fractures, with high morbidity and mortality in aging population. Efficacy of anti-osteoporotic treatment is based on drug potency but also on compliance and persistence to treatment regimen, which is very low, as already described for other diseases. Teriparatide (TPTD) is the first anabolic agent developed for the treatment of osteoporosis. Since it appears that persistence to Teriparatide declines over time, aim of this pilot multicenter observational study was to evaluate persistence and adherence to TPTD (20 μg daily injection regimen for 18 months) treatment (PATT) in patients affected by severe osteoporosis in an every day clinical practice. Patients affected by severe osteoporosis were selected among those who referred to 5 different specialized centers for osteoporosis in North, Center and South of Italy. A sample of 475 women with severe postmenopausal osteoporosis treated with TPTD in accordance to the Italian osteoporosis guidelines was included. At the beginning of TPTD treatment patients were instructed on the use of the device by the referring specialist of the center, a resident fellow or a nurse. Bone biochemical markers were evaluated the same morning and after 1, 3, 6, 12 and 18 months. Patients were visited at time 0 and after 6, 12 and 18 months for clinical follow up. The results included observations of 441/475 patients (98% women) who completed the 18 months treatment; mean age for women was 73±8 and for men 65±9. After 6 months of TPTD treatment persistence was of 89,79%, 87,75% after 12 months and 86,85% after 18 months. Adherence was of 100% at 6,12 and 18 months. Total dropouts were 13,15% (71/441), which was usually higher within the first 6 months of TPTD treatment. Most common adverse events (arthralgies 2,7%, dizziness 1,8%, migraine 1,8%, depression 1,6%, hypertension 1,1%) were reported in 62/441 patients (14%) of patients, but were not reason for stopping treatment. The persistence and adherence to TPTD treatment obtained in this multicenter observational real life study was very high as compared to studies performed by others. These encouraging results suggest that different key factors such quality of information, frequency of visits, motivations given to patients, opportunity to call the doctor might play a pivotal role in the high persistence and adherence to TPTD treatment obtained in our study and need to be carefully considered before prescribing chronic anti-osteoporotic therapy.