Drugs For Treatment Of Osteoporosis Research Articles

New Targets and Emergent Therapies for Osteoporosis.

The 11 existing FDA-approved osteoporosis drug treatments include hormone replacement therapy, 2 SERMs (raloxifene and bazedoxifene), 5 inhibitors of bone-resorbing osteoclasts (4 bisphosphonates and anti-RANKL denosumab), 2 parathyroid hormone analogues (teriparatide and abaloparatide), and 1 WNT signaling enhancer (romosozumab). These therapies are effective and provide multiple options for patients and physicians. As the genomic revolution continues, potential novel targets for future drug development are identified. This review takes a wide perspective to describe potentially rewarding topics to explore, including knowledge of genes and pathways involved in bone cell metabolism, the utility of animal models, targeting drugs to bone, and ongoing advances in drug design and delivery.

Use of antiosteoporotic drugs and calcium/vitamin D in patients with fragility fractures: impact on re-fracture and mortality risk.

To evaluate the impact of pharmacological treatment in osteoporosis patients with recent fracture and to assess the incidence of subsequent fracture and all-cause mortality. This observational retrospective study was based on data from administrative databases of five Italian Local Health Units. Osteoporosis patients aged ≥ 50 years with hospitalization for vertebral or hip fracture occurring between 01/01/2011 and 31/12/2015 were included. Treatment adherence was calculated using the medication possession ratio. Multivariable proportional hazard Cox model was used to identify factors associated with time to re-fracture and all-cause mortality. A cohort of 3475 patients were included and 41.5% of them did not receive any specific anti-fracture treatment. Among treated patients (N = 2032), the majority (83.6%) received calcium/vitamin D supplementation. Over a mean follow-up of 3 years, the risk of subsequent fractures was 44.4% lower in treated patients compared to untreated ones (HR = 0.556, 95% CI = 0.420-0.735, p < 0.001) and 64.4% lower in those receiving calcium/vitamin D supplementation compared to osteoporosis treatment only (HR = 0.356, 95% CI = 0.237-0.533, p < 0.001). The risk of re-fracture was 77.2% lower in treated patients who were adherent to medication (HR = 0.228, 95% CI = 0.139-0.376, p < 0.001). Treated patients had 64% lower mortality risk over the follow-up compared to untreated ones (HR = 0.360, 95% CI = 0.310-0.418, p < 0.001). A consistent proportion of osteoporosis patients did not receive specific treatment after a fracture, showing poor adherence to national guidelines on osteoporosis treatment. Osteoporosis drug treatment, and to a greater extent in combination with calcium/vitamin D, and adherence were correlated with lower risk of both re-fracture and all-cause mortality.

Cumulative network-meta-analyses, practice guidelines and actual prescriptions of drug treatments for postmenopausal osteoporosis: a study protocol for cumulative network meta-analyses and meta-epidemiological study

IntroductionCumulative network meta-analysis (NMA) is a method to provide a global comparison of multiple treatments with real-time update to evidence users. Several studies investigated the ranking of cumulative NMA and...

Beneficial effects of hyperoside on bone metabolism in ovariectomized mice

Hyperoside, an active flavonoid glycoside isolated from many traditional Chinese medicines, has received much attention because of its potential role in osteoporosis treatment. In the present study, we investigated the antiosteoporotic role and mechanism of hyperoside on ovariectomized (OVX) mice. Sixty female Kunming mice received one of three treatments orally for 12 weeks: estradiol valerate (0.3 mg/kg body weight/day), hyperoside (20, 40, or 80 mg/kg body weight/day), or vehicle. We found that hyperoside was effective in preventing osteoporosis by increasing bone mineral density, restoring trabecular bone micro-architecture, and enhancing bone strength. Meanwhile, the activities of bone resorption markers, including tartrate-resistant acid phosphatase 5b (TRAP-5b) and C-terminal telopeptide of type I collagen (CTX), were significantly decreased, while the bioactivity of bone formation markers, osteocalcin (OC) and bone-specific alkaline phosphatase (BALP), were significantly increased. Mechanistically, hyperoside reduced the expression of receptor activator of nuclear factor-κB ligand (RANKL), TNF-receptor-associated factor 6 (TRAF6), phosphorylated inhibitor of nuclear factor-κB α (IκBα), NF-kB p65, and nuclear factor of activated T cell cytoplasmic 1 (NFATc1) and promoted the expression of osteoprotegerin (OPG). Therefore, the function of hyperoside might be related to the inhibition of the TRAF-6 mediated RANKL/RANK/NF-κB signaling pathway and the elevation of the OPG/RANKL ratio. These data demonstrated that hyperoside has potential applications as a drug for osteoporosis treatment.

Effects of osteoporosis drug treatments on cortical and trabecular bone in the femur using DXA-based 3D modeling.

The aim of the present study was to assess the effects of osteoporosis drugs on cortical and trabecular bone at the proximal femur using DXA-based 3D modeling. We retrospectively analyzed 155 patients stratified by treatments: naive of treatment (NAIVE), alendronate (AL), denosumab (DMAB), and teriparatide (TPTD). DXA scans were performed at baseline and after treatment, and areal bone mineral density at spine and femur were measured. A software algorithm (3D-SHAPER) was used to derive 3D models from hip DXA scans and compute: trabecular and cortical volumetric BMD (vBMD), cortical thickness (Cth), and cortical surface BMD (cortical sBMD). Changes from baseline were normalized at 24months and evaluated in terms or percentage. After 24months, a non-significant decrease was observed for trabecular vBMD, Cortical sBMD, Cth, and cortical vBMD (- 2.3, - 0.8, - 0.3, and - 0.5%) in the NAIVE group. Under AL and DMAB, significant increases were observed in trabecular vBMD (3.8 and 7.3%), cortical vBMD (1.4 and 2.0%), and cortical sBMD (1.5 and 3.6%). An increase in Cth was observed in patients under DMAB (1.8%). Under TPTD, a significant increase in Trabecular vBMD was observed (5.9%) associated with a non-significant increase of Cth (+ 1%) concomitant with a decrease in cortical vBMD (- 1.1%). Results obtained in this head-to-head study are consistent with those obtained using computed tomography in the literature. DXA-based modeling techniques could complement standard DXA examination to monitor treatment effects on trabecular and cortical compartments.

Cost-effectiveness of osteoporosis screening strategies for hip fracture prevention in older Chinese people: a decision tree modeling study in the Mr. OS and Ms. OS cohort in Hong Kong.

To examine the cost-effective potential osteoporosis screening strategies for hip fracture prevention in Hong Kong. Decision tree models were constructed to evaluate the cost per quality-adjusted life years (QALYs) of the different osteoporosis screening strategies followed by subsequent 5-year treatment with alendronate compared to no screening (but treat if a hip fracture occurs). The multiple osteoporosis screening strategies were composed of alternative tests and initiation age groups were evaluated with a 10-year horizon, and treatment were assigned if central dual-energy X-ray absorptiometry (DXA) T-score (at either the hip or spine) is - 2.5 or less. Strategies included DXA for all people and pre-screening with the Fracture Risk Assessment Tool (FRAX) at specific thresholds or by calcaneal quantitative ultrasonography (QUS) before taking DXA examination. All the model inputs were based on the Mr. OS and Ms. OS Hong Kong cohort; data are obtained from the Social Welfare Department or the published literature. All of the screening strategies, including the universal screening with DXA and the pre-screening with FRAX or QUS before DXA, were consistently more cost-effective than no screening for people aged 65years old or over. One-way sensitivity analysis with a more optimistic assumption on treatment adherence or inclusion of other major osteoporotic fractures did not change the results materially. Probabilistic sensitivity analyses showed a dominant role of pre-screening with FRAX followed by subsequent osteoporosis drug treatment in people aged 70years old or over in Hong Kong. Osteoporosis screening strategies based on DXA with or without pre-screening are more cost-effective compared to no screening for Chinese people aged 65 or over in Hong Kong.

Postmenopausal osteoporosis

Introduction. Postmenopausal women are at a great risk for osteoporosis and bone fractures. Pathophysiology of osteoporosis. The two main factors causing osteoporosis are aging and loss of the gonadal function. Postmenopausal osteoporosis is primarily the consequence of estrogen deficiency, whereas senile osteoporosis is related to the natural aging process. Risk factors for the onset of osteoporosis. Risk factors include: age of 50 years and over. female gender. Caucasian race, genetic predisposition, short stature, under?nourishment, physical inactivity, amenorrhea, late menarche, early menopause, estrogen and androgen deficiency, alcohol consumption, cigarette smoking, calcium deficiency in the diet, use of some drugs. Osteoporosis complications. Osteoporosis is the main cause of bone fractures in older population. Biochemical indicators of bone metabolism. A great number of bone formation and resorption markers are listed. Diagnostics. Dual-energy X-ray absorptiometry measurements of the hip and spine are a worldwide standard in diagnosing osteoporosis. Dual X-ray laser heel measurement is an alternative to dual-energy X-ray absorptiometry. Quantitative computed tomography measures thin layers by cross-sectional scans. Quantitative ultrasonography is a good method, but the measurements are not as precise as by other imaging techniques. Drug treatment of osteoporosis. Modern treatment of osteoporosis includes application of bisphosphonates, selective estrogen-receptor modulators, calcium preparations, vitamin D, monoclonal antibodies, hormonal therapy, estrogens, and phytoestrogens. Prevention. Lifestyle changes and non-pharmacological measures are most important for healthy bones. Physical activity, nutrition rich in calcium and vitamin D, avoidance of smoking and alcohol consumption are of crucial importance for people of all ages. especially for the older ones.

Management of osteoporosis after fragility fractures

Osteoporosis is defined as asystemic bone disease with decreased bone strength and an increased susceptibility for fractures. Older people in particular face an increased risk of fractures. These kind of fractures are usually caused by an inadequate trauma and are the so-called fragility fractures. In older adults immediate fracture stabilization and early mobilization have become the standard procedure after afragility fracture. Treatment of the underlying osteoporosis often plays aminor role in clinical practice. Only asmall group of patients are already under osteoporosis medication and even after afracture occurs only few patients receive osteoporosis drug treatment with the aim to reduce the progression of osteoporosis and to reduce subsequent fractures. In the literature this has been described as the osteoporosis care gap. The following article presents an overview of treatment options and answers many different questions from the clinical routine.

Comment on: Patients' preferences for anti-osteoporosis drug treatment: a cross-European discrete choice experiment: reply.

_SIR,_ We are grateful to Dr Armstrong for sharing his views and concerns about our recent paper that elicited patients’ preferences for osteoporosis drug treatment using a cross-European discrete-choice experiment (DCE). First, the correspondent questioned the use of DCE in the area of osteoporosis therapy. Although the application of DCEs within healthcare is relatively new, DCEs are nowadays increasingly used to elicit preferences for various healthcare conditions and purposes. Previous DCEs were already conducted in osteoporosis, suggesting that respondents were able to discriminate between medication attributes and that a DCE could be suitable in the area of osteoporosis. Our study confirms this finding. [...]

Osteoporosis drug treatment: duration and management after discontinuation. A position statement from the SVGO/ASCO.

Antiosteoporotic drugs are recommended in patients with fragility fractures and in patients considered to be at high fracture risk on the basis of clinical risk factors and/or low bone mineral density. As first-line treatment most patients are started with an antiresorptive treatment, i.e. drugs that inhibit osteoclast development and/or function (bisphosphonates, denosumab, oestrogens or selective oestrogen receptor modulators). In the balance between benefits and risks of antiresorptive treatment, uncertainties remain regarding the optimal treatment duration and the management of patients after drug discontinuation. Based on the available evidence, this position statement will focus on the long-term management of osteoporosis therapy, formulating decision criteria for clinical practice.

Public priorities for osteoporosis and fracture research: results from a general population survey

SummaryThis is the first national study of public and patient research priorities in osteoporosis and fracture. We have identified new research areas of importance to members of the public, particularly ‘access to information from health professionals’. The findings are being incorporated into the research strategy of the National Osteoporosis Society.PurposeThis study aimed to prioritise, with patients and public members, research topics for the osteoporosis research agenda.MethodsAn e-survey to identify topics for research was co-designed with patient representatives. A link to the e-survey was disseminated to supporters of the UK National Osteoporosis Society (NOS) in a monthly e-newsletter. Responders were asked to indicate their top priority for research across four topics (understanding and preventing osteoporosis, living with osteoporosis, treating osteoporosis and treating fractures) and their top three items within each topic. Descriptive statistics were used to describe demographics and item ranking. A latent class analysis was applied to identify a substantive number of clusters with different combinations of binary responses.ResultsOne thousand one hundred eighty-eight (7.4%) respondents completed the e-survey. The top three items overall were ‘Having easy access to advice and information from health professionals’ (63.8%), ‘Understanding further the safety and benefit of osteoporosis drug treatments’ (49.9%) and ‘Identifying the condition early by screening’ (49.2%). Latent class analysis revealed distinct clusters of responses within each topic including primary care management and self-management. Those without a history of prior fracture or aged under 70 were more likely to rate items within the cluster of self-management as important (21.0 vs 12.9 and 19.8 vs 13.3%, respectively).ConclusionThis is the first study of public research priorities in osteoporosis and has identified new research areas of importance to members of the public including access to information. The findings are being incorporated into the research strategy of the National Osteoporosis Society.

Monthly oral ibandronate 100mg is as effective as monthly intravenous ibandronate 1mg in patients with various pathologies in the MOVEST study.

The non-inferiority of oral ibandronate 100mg to intravenous (i.v.) ibandronate 1mg in increasing lumbar spine (LS) bone mineral density (BMD) after 12months of treatment was demonstrated in the randomized, phase III MOVEST study. We conducted subgroup analyses in the per-protocol set of the study (n=183 oral ibandronate; n=189 i.v. ibandronate). In patients with LS BMD T score ≥ -3.0 or < -3.0 at screening, LS BMD gains from baseline were 4.42 and 5.79%, respectively, with oral ibandronate, and 4.60 and 5.83%, respectively, with i.v. ibandronate. LS BMD gains in patients with or without prevalent vertebral fractures were 5.21 and 5.23%, respectively, with oral ibandronate, and 5.01 and 5.49%, respectively, with i.v. ibandronate. In patients aged <75 or ≥75years, LS BMD gains were 5.46 and 4.51%, respectively, with oral ibandronate, and 5.25 and 5.77%, respectively, with i.v. ibandronate. LS BMD gains in patients with baseline 25-hydroxyvitamin D levels ≥20 or <20ng/mL were 5.35 and 4.76%, respectively, with oral ibandronate, and 5.05 and 6.57%, respectively, with i.v. ibandronate. Similar results were obtained in patients with or without prior bisphosphonate (BP) treatment, and in those receiving osteoporosis drug treatment other than BPs. In conclusion, oral ibandronate 100mg demonstrated comparable BMD gains with monthly i.v. ibandronate, and thus shows high utility in the lifestyle and disease conditions associated with osteoporosis in Japanese patients.

Cytoprotective effect of chlorogenic acid against hydrogen peroxide-induced oxidative stress in MC3T3-E1 cells through PI3K/Akt-mediated Nrf2/HO-1 signaling pathway.

Osteoporosis is a disorder of bone and its development is closely associated with oxidative stress and reactive oxygen species (ROS). Chlorogenic acid (CGA) has potential antioxidant effects and its pharmacological action in osteoblasts is not clearly understood. The present study aimed to clarify the protective effects and mechanisms of CGA on hydrogen peroxide (H2O2)-induced oxidative stress in osteoblast cells. MC3T3-E1 cells were treated with H2O2 to induce oxidative stress model in vitro. Cells were treated with CGA prior to H2O2 exposure, the intracellular ROS production, malondialdehyde content, nitric oxide release and glutathione level were measured. We also investigated the protein levels of heme oxygenase-1 (HO-1), the nuclear translocation of transcription factor NF-erythroid 2-related factor (Nrf2) and the phosphorylation levels of Akt in CGA-treated cells. The results showed that pretreatment of CGA could reverse the inhibition of cell viability and suppress the induced apoptosis and caspase-3 activity. Additionally, it significantly reduced H2O2-induced oxidative damage in a dose-dependent manner. Furthermore, it induced the protein expression of HO-1 together with its upstream mediator Nrf2, and activated the phosphorylation of Akt in MC3T3-E1 cells. LY294002, a PI3K/Akt inhibitor, significantly suppressed the CGA-induced Nrf2 nuclear translocation and HO-1 expression. Reduction of cell death mediated by CGA in presence of H2O2 was significantly inhibited by Zinc protoporphyrin IX (a HO-1 inhibitor) and LY294002. These data demonstrated that CGA protected MC3T3-E1 cells against oxidative damage via PI3K/Akt-mediated activation of Nrf2/HO-1 pathway, which may be an effective drug in treatment of osteoporosis.

4. The Low-Intensity Pulsed Ultrasound (LIPUS) Mechanism and the Effect of Teriparatide on Fracture Healing.

Low-Intensity Pulsed Ultrasound (LIPUS) provided a mechanical stimulus, and was thought to promote fracture healing by signal transduction through integrin, a cytoskeletal protein. Meanwhile, teriparatide, a drug for osteoporosis treatment, showed efficacy in promoting bone metabolism. This drug also appeared to prevent fractures in patients with serious osteoporosis by improving bone mineral density and bone quality, which in turn resulted from promoting action for bone metabolism. Further, clinical trials and fundamental research reported that teriparatide demonstrated the effect of promoting fracture healing. Mechanical stimulus by LIPUS had a topical effect on fractures; on the other hand, teriparatide (peptide hormone) had both topical and systemic effects. Both LIPUS and teriparatide had the effect of fracture healing, but it was supposed that the characteristics of each effect were different because of the different mechanism of action. Moreover, the combination therapy of LIPUS and teriparatide was expected to produce synergies. We used elderly rats as models for the femoral fracture to examine the effects of LIPUS and teriparatide on promoting fracture healing for treatment delay by aging. We observed the fracture healing process in 40-week-old rats as an elderly model using simple radiographs, and recognized a delay in fracture healing compared with that of 8-week-old rats. As discussed in histomorphology, it was demonstrated that the period of endochondral ossification, from chondrogenesis to teleost cross-linked callus, was prolonged and the fracture healing process was delayed by aging. Next, we treated the elderly fracture models with LIPUS for 20 minutes a day from the first day after the fracture, and compared them with non-treated models. The bone unions of the treated models were observed earlier than those of non-treated models in the simple radiographs. LIPUS shortened the period of endochondral ossification. Further, we gave the elderly fracture models teriparatide subcutaneously 5 μg/kg three times a week from the first day after the fracture. Bone unions of the treated models were observed earlier than those of non-treated models in simple radiographs as well. In micro CT analysis, it was demonstrated that lamellar bone transforming and bone remodeling of the trabecular structure of external callus were especially accelerated. The results of these trials showed that both LIPUS and teriparatide demonstrated the effect of promoting fracture healing, and each had unique characteristics.

Patient acceptance of osteoporosis treatment: Application of the stages of change model

ObjectivesTo examine whether a commonly used model of behaviour change, stages of change, is helpful in understanding osteoporosis treatment initiation in a cohort of fragility fracture patients. Study designThis longitudinal cohort study used data from a provincial osteoporosis screening program targeting fragility fracture patients age 50 and over. Logistic regression was used to identify baseline factors associated with patients moving from the first, pre-contemplation stage at baseline to the more advanced stages of action/maintenance at follow-up, when treatment is initiated and maintained. Main outcome measurePatient’s stage-of-change readiness to accept osteoporosis treatment. ResultsAt baseline, 91% of patients were in the pre-contemplation stage. Of these, 74.1% remained at the same stage at follow-up, 2.7% moved to contemplation and preparation while 23.2% moved to action/maintenance. The adjusted analysis showed that those who moved from pre-contemplation to action/maintenance were more likely to have a previous fracture OR 1.5 (1.1–2.0), history of oral steroid use OR 2.1 (1.3–3.5), higher perceived benefits to osteoporosis drug treatment OR 1.2 (1.0–1.3), perception of bones as “thin” OR 2.8 (2.0–4.0) and were less likely to perceive that they were taking too many medications OR 0.6 (0.5–0.9). ConclusionsWith the majority of patients in the pre-contemplation and the action/maintenance stages, our results suggest an existence of a two-stage model. The baseline factors that we identified can be used to predict which patients are less likely to initiate treatment, which in turn, can be used to inform post-fracture interventions and facilitate behaviour change.

Understanding the pathogenesis of hip fracture in the elderly, osteoporotic theory is not reflected in the outcome of prevention programmes.

Hip fractures are an acute and worsening public health problem. They mainly affect elderly people, a population group that is highly vulnerable to disease and accidents, and to falls in particular. Although it has been suggested that osteoporosis is the cause of hip fractures, they mainly occur after a fall has been suffered. The underlying causes of a fall are not related to osteoporosis, although pharmaceutical companies have coined the term "osteoporotic fracture" for hip fractures in the elderly. Drug treatments for osteoporosis have not diminished the frequency of these injuries, nor have they prevented the occurrence of a subsequent fracture. Since pharmaceutical interests require osteoporosis to be considered a disease, rather than a normal condition of senescence, they go further by assuming that treatment for osteoporosis is essential, and that this policy will diminish the incidence of hip fractures. On the other hand, the origin and treatment of conditions that may be conducive to provoking falls are very difficult to elucidate. In this paper, we consider some of the medical and social problems that arise in this area, as well as conflicts of interest regarding the aetiopathogenesis and prevention of hip fracture, and propose a new paradigm for the prevention of falls.

A Review of Patient Preferences for Osteoporosis Drug Treatment.

Poor medication adherence is a major problem in chronic diseases such as osteoporosis that may partially be due to unaddressed patient values and preferences. Data on patient preferences could help clinicians to improve medication adherence and could also be useful in policy decisions and guideline development. This paper aims to identify literature reporting on the preferences of patients for osteoporosis drug medications. Several methods have been used to elicit patient preferences for medications and their characteristics including qualitative research, survey with ranking/rating exercises, discrete-choice experiments and clinical studies (crossover designs, open-label study). All these studies revealed that osteoporotic patients have preferences for medications and their attributes, in particular for less-frequent dosing regimens. Interestingly, variations in the preferences of patients were observed in most studies, suggesting the importance to take into account individual preference in decision-making to improve osteoporosis care.

Inadequate management for secondary fracture prevention in patients with distal radius fracture by trauma surgeons.

We evaluated the secondary fracture prevention in 1445 patients with distal radius fracture by trauma surgeons. The rate of patients with distal radius fracture who underwent bone mineral density (BMD) examination was low, suggesting that appropriate treatment for osteoporosis by trauma surgeons is not performed at present. To clarify the status of osteoporosis interventions after distal radial fractures by trauma surgeons who play the main role in treatment for these fractures, we performed a survey involving multiple institutions in Japan. We asked 155 board members of the Japanese Society for Fracture Repair for their cooperation and performed a survey in 48 institutions with which members who gave cooperation were affiliated. The subjects consisted of consecutive patients with distal radial fractures occurring between January and December 2012. The presence or absence of a diagnosis of osteoporosis and bone mineral density examination after fracture was investigated. A total of 1445 patients with distal radial fractures were evaluated in this study. BMD examination for diagnosis and treatment for osteoporosis after fracture was performed respectively in 126 (8.7%) and 193 (13.4%) of 1445 patients. Treatment for osteoporosis was performed in 93 (73.8%) of 126 patients who underwent BMD examination after fracture and 100 (8.2%) of 1219 who did not undergo BMD examination. Of the 126 patients who underwent BMD examination after fracture, 89 showed a BMD <80% of the young adult mean as a criterion for the initiation of drug treatment for osteoporosis in Japan and 77 (86.5%) of the 89 patients were treated with drugs. The rate of patients with distal radial fractures who underwent BMD examination was low, suggesting that appropriate treatment for osteoporosis by trauma surgeons is not performed at present.

Regional variability in changes in the incidence of hip fracture in the Spanish population (2000–2012)

The objective is to analyse the evolution of the incidence of hip fracture in the female population of Spain from 2000 to 2012 and to establish the possible changes which may have been seen over this period of time, including the trends in the different regions of the country. Fragility-related hip fractures are considered to be the fractures of greatest significance to public health due to their high degree of morbidity and mortality. The change in their incidence, both in absolute values and when adjusted for age, is the subject of debate. The objective of this article is to describe the changes in the rates of hip fracture in Spain by autonomous community between the years 2000 and 2012. Using the data from the Spanish Minimum Basic Data Set, in which are all the recorded cases of women with a principal diagnosis of hip fracture, the incidence rates by age group and by autonomous community were obtained. Poisson distribution or negative binomial regressions were carried out to estimate the average annual change over the time period analysed. There have been statistically significant changes in the trends of rates of incidence for all age groups of women over 65 years of age. The annual reduction was 2.2% for women of 65-74 years of age and less for those between 75 and 84. The rates of incidence for those over 85 increased annually by 0.58%. Hip fractures continue to increase in absolute numbers, although if the rates are adjusted for age, a downward trend is seen in certain age groups. These findings have various origins, although in the absence of great changes in population structure, we believe that drug treatments for osteoporosis may play a role. There is variability in the change in incidence of hip fractures in different parts of the country. Further studies are required to be able to identify the causes.

Characteristics of local human skeleton responses to microgravity and drug treatment for osteoporosis in clinic

Analysis of the results of long-term investigations of bones in cosmonauts flown on the orbital station MIR and International space station (n = 80) was performed. Theoretically predicted (evolutionary predefined) change in mass of different skeleton bones was found to correlate (r = 0.904) with position relatively the Earth's gravity vector. Vector dependence of bone loss ensues from local specificity of expression of bone metabolism genes which reflects mechanic prehistory of skeleton structures in the evolution of Homo erectus. Genetic polymorphism is accountable for high individual variability of bone loss attested by the dependence of bone loss rate on polymorphism of certain bone metabolism markers. Parameters of one and the other orbital vehicle did not modulate individual-specific stability of the bone loss ratio in different segments of the skeleton. This fact is considered as a phenotype fingerprint of local metabolism in the form of a locus-unique spatial structure of distribution of noncollagenous proteins responsible for position regulation of endosteal metabolism. Drug treatment of osteoporosis (n = 107) evidences that recovery rate depends on bone location; the most likely reason is different effectiveness of local osteotrophic intervention into areas of bustling resorption.