The effect of drugs on implant osseointegration- A narrative review.

OBJECTIVE: This narrative review aims to investigate the effects of drugs on implant osseointegration, analyzing their potential positive or negative impact on the direct structural and functional connection between bone and load-carrying implants. BACKGROUND: The review seeks to provide a comprehensive understanding of osseointegration, which refers to the successful integration of an implant with living bone, resulting in no progressive relative movement between them. Exploring the effects of drugs on implant osseointegration is crucial for optimizing outcomes and enhancing patient care in orthopedic implant procedures. METHODS: Relevant studies on the effects of drugs on implant osseointegration were identified through a literature search. Electronic databases, including PubMed, Embase, and Google Scholar, were utilized, employing appropriate keywords and MeSH terms related to osseointegration, implants, and drug interventions. The search was limited to English studies. DISCUSSION: This overview presents a detailed analysis of the effects of drugs on implant osseointegration. It explores drugs such as bisphosphonates, teriparatide, statins, angiotensin-converting enzyme inhibitors, beta-blockers, nitrites, and thiazide diuretics as promoters of osseointegration. Conversely, loop diuretics, non-steroidal anti-inflammatory drugs, corticosteroids, cyclosporine A, cisplatin, methotrexate, antibiotics, proton pump inhibitors (PPIs), antiepileptics, selective serotonin reuptake inhibitors (SSRIs), and anticoagulants are discussed as inhibitors of the process. The role of vitamin D3 remains uncertain. The complex relationship between drugs and the biology of implant osseointegration is emphasized, underscoring the need for further in vitro and in vivo studies to validate their effects CONCLUSION: This narrative review contributes to the literature by providing an overview of the effects of drugs on implant osseointegration. It highlights the complexity of the subject and emphasizes the necessity for more extensive and sophisticated studies in the future. Based on the synthesis of the reviewed literature, certain drugs, such as bisphosphonates and teriparatide, show potential for promoting implant osseointegration, while others, including loop diuretics and certain antibiotics, may impede the process. However, additional research is required to solidify these conclusions and effectively inform clinical practice.

Second hip fracture in older adults: incidence and risk factors.

PURPOSE: A second hip fracture can occur in older adults who have already suffered an initial hip fracture. The aim of this study was to determine the incidence, mortality and risk factors for second hip fractures in older adults with hip fractures. METHODS: Between 2009 and 2019, 2013 patients (mean age: mean age 76.5 ± 5.4 SD) who were admitted to a tertiary care hospital for a hip fracture surgery were retrospectively analyzed. The patients were divided into two groups: those with a second hip fracture and those without a second hip fracture within the following two years after the initial fracture. RESULTS: 321 patients (15.9%, mean age: 85.3 ± 4.9 SD) sustained a second contralateral hip fracture, the first two years after the initial hip fracture whereas 136 patients (6.8%) sustained a contralateral hip fracture within 12 months. In total 274 (13.6%) died in the first two years after the initial hip fracture; among these, 139 patients (43.3%) had a contralateral second hip fracture. The mean time from the first hip fracture to second hip fracture was 13.2 ± 7.6 months. The advance age, female gender, living alone, dementia, chest and urinary tract infection, chronic heart failure, peripheral vascular disease were identified as risk factors for a second contralateral hip fracture. CONCLUSIONS: Identifying risk factors for a second contralateral hip fracture can be particularly helpful in providing focused medical assistance.

The Superiority of Zoledronic Acid Over Risedronate for Paget's Disease: A 16-Year Experience at a Single Institution.

Introduction Bisphosphonates are considered to be the treatment of choice for patients with active Paget's disease. The aim of this study was to record and assess the therapeutic effect in response to a single intravenous infusion of 5mg zoledronic acid or oral risedronate. Methods A retrospective observational study was conducted of 89 patients in Greek patients with active Paget's disease from a tertiary hospital in North Greece. Patients were treated with either a single intravenous infusion of 5mg zoledronic acid (1st group, n=46) or 30mg of risedronate per day for 60 days (2nd group, n=43). All patients received 1000mg of calcium and 400-800IU of calciferol daily. The primary outcome measure was to record the therapeutic response defined as the control of patients' symptoms and normalization of the biochemical markers of bone metabolism. The secondary outcome measures included the patient's quality of life which was evaluated by the questionnaire SF-36 and adverse events. Results Forty patients from the zoledronic acid group and 38 patients from the risedronate group, who reported pain at the beginning of the study, showed a significant degree of clinical improvement. All the patients in our study showed a therapeutic response at six months while the remission was persistent at 36 months. There was a statistically significant difference between pre-treatment basal results and values at the sixth and 36th months of treatment (p<0.001) between the two groups. Conclusion The study demonstrated the superiority of zoledronic acid over risedronate in patients with active Paget's disease.

Change in BMI affects the risk of falling in postmenopausal osteopenic and osteoporotic women.

OBJECTIVES: To investigate the impact of the body mass index (BMI) change on risk of falling in postmenopausal women with osteopenia or osteoporosis. Also, we aimed to evaluate and associate the individuals' functionality, mobility and balance with the risk of falling. METHODS: This one-year prospective observational study assessed 498 postmenopausal Greek women over the 50th year of age suffering from either osteoporosis or osteopenia. Parameters such as the height, weight and BMI were documented. Furthermore, the subjects were asked whether they experienced a fall the preceding year. Balance was evaluated using the Berg Balance Scale, the Timed-Up-And-Go test, and the 30 Seconds Sit-to-Stand test. Hand-grip strength was assessed with the Jamar Hydraulic Hand Dynamometer. RESULTS: The observed one-year BMI change was associated with falls in postmenopausal osteopenic and osteoporotic women over the age of 70. Additionally, there were statistically significant changes in the BBS, TUG, 30CST and the hand-grip strength on both hands at the one-year follow-up but there were not associated with an increased fall risk. CONCLUSION: The one-year change in BMI was associated with the risk of falling in postmenopausal osteopenic and osteoporotic women over the 70th year of age. Whereas, the one-year change in balance, mobility and grip strength were not linked to an increased risk of falling.

Change in kyphosis does not affect the risk of falling in postmenopausal osteopenic and osteoporotic women.

OBJECTIVES: To examine the influence of the annual change in kyphosis on the risk of falling in postmenopausal osteopenic and osteoporotic women. METHODS: This prospective observational study included 498 postmenopausal Greek women over the age of 50, suffering from either osteoporosis or osteopenia. Data on age, height, weight, and self-reported falls were collected. Additionally, we evaluated the degree of the kyphosis angle, the balance, the mobility, the functionality and the handgrip strength on both hands of each subject using the Debrunner kyphometer, the Berg Balance Scale, the Timed-Up-and-Go test, the 30 Seconds Sit-to-Stand test and the Jamar Hydraulic Hand Dynamometer, respectively. All the above data were recorded at the baseline visit and the 12-month follow-up visit for each participant. RESULTS: All examined variables presented a statistically significant change at the 12-month follow-up visit. Nevertheless, the annual change in kyphosis did not show any association with the risk of falling. CONCLUSION: No association was shown between the annual change in kyphosis and the risk of falling in postmenopausal osteopenic and osteoporotic women, nor bears any substantial prognostic value for future falls.

Bone metabolism subgroups identified as hip fracture patients via clustering.

PURPOSE: The aim of the study was to describe the bone metabolism status that underlies a hip fracture. METHODS: Estimated glomerular filtration rate (e-GFR), calcium (Ca), phosphorus (P), total (ALP) and bone specific alkaline phosphatase (b-ALP), intact parathyroid hormone (i-PTH), 25-hydroxy-vitamin D (25OHD), total procollagen type I amino-terminal propeptide (PINP), and N-terminal peptide of collagen I (NTx), measured at admission in 272 hip fracture patients, were ex post analyzed by K-means clustering and principal component analysis and were evaluated by a clinician. RESULTS: Four components, mainly consisting of b-ALP, PINP, ALP, and NTx; e-GFR and P; i-PTH and 25OHD; and Ca explained about 70% of the variability. A total of 184 patients clustered around a centroid (A) with low 25OHD (13.2 ng/ml), well-preserved kidney function (e-GFR=67.19 ml/min/1.73m2), normal Ca, P, i-PTH and bone markers, with the exception of slightly increased NTx (24.82nMBCE). Cluster B (n=70) had increased i-PTH (93.38 pg/ml), moderately decreased e-GFR, very low 25OHD (8.68 ng/dl), and high bone turnover (b-ALP 28.46 U/L, PINP 69.87 ng/ml, NTx 31.3nMBCE). Cluster C (n=17) also had hyperparathyroidism (80.35 pg/ml) and hypovitaminosis D (9.15 ng/ml), low e-GFR(48.89 ml/min/1.73m2), and notably high ALP (173 U/L) and bone markers (b-ALP 44.64 U/L, PINP 186.98 ng/ml, NTx 38.28nMBCE). According to the clinician, 62 cases clearly had secondary hyperparathyroidism. CONCLUSIONS: Based on serum measurements, the dominant patterns of bone metabolism were normal bone turnover with high normal NTx, and secondary hyperparathyroidism related to chronic kidney disease and hypovitaminosis D. The bone formation markers, e-GFR, NTx, and P composed the most important factors.

Secondary Fracture Prevention: Consensus Clinical Recommendations from a Multistakeholder Coalition.

Osteoporosis-related fractures are undertreated, due in part to misinformation about recommended approaches to patient care and discrepancies among treatment guidelines. To help bridge this gap and improve patient outcomes, the American Society for Bone and Mineral Research assembled a multistakeholder coalition to develop clinical recommendations for the optimal prevention of secondary fractureamong people aged 65 years and older with a hip or vertebral fracture. The coalition developed 13 recommendations (7 primary and 6 secondary) strongly supported by the empirical literature. The coalition recommends increased communication with patients regarding fracture risk, mortality and morbidity outcomes, and fracture risk reduction. Risk assessment (including fall history) should occur at regular intervals with referral to physical and/or occupational therapy as appropriate. Oral, intravenous, andsubcutaneous pharmacotherapies are efficaciousandcanreduce risk of future fracture.Patientsneededucation,however, about thebenefitsandrisks of both treatment and not receiving treatment. Oral bisphosphonates alendronate and risedronate are first-line options and are generally well tolerated; otherwise, intravenous zoledronic acid and subcutaneous denosumab can be considered. Anabolic agents are expensive butmay be beneficial for selected patients at high risk.Optimal duration of pharmacotherapy is unknown but because the risk for second fractures is highest in the earlypost-fractureperiod,prompt treatment is recommended.Adequate dietary or supplemental vitaminDand calciumintake shouldbe assured. Individuals beingtreatedfor osteoporosis shouldbe reevaluated for fracture risk routinely, includingvia patienteducationabout osteoporosisandfracturesandmonitoringfor adverse treatment effects.Patients shouldbestronglyencouraged to avoid tobacco, consume alcohol inmoderation atmost, and engage in regular exercise and fall prevention strategies. Finally, referral to endocrinologists or other osteoporosis specialists may be warranted for individuals who experience repeated fracture or bone loss and those with complicating comorbidities (eg, hyperparathyroidism, chronic kidney disease).

Secondary Fracture Prevention: Consensus Clinical Recommendations from a Multistakeholder Coalition.

Osteoporosis-related fractures are undertreated, due in part to misinformation about recommended approaches to patient care and discrepancies among treatment guidelines. To help bridge this gap and improve patient outcomes, the American Society for Bone and Mineral Research assembled a multistakeholder coalition to develop clinical recommendations for the optimal prevention of secondary fracture among people aged 65 years and older with a hip or vertebral fracture. The coalition developed 13 recommendations (7 primary and 6 secondary) strongly supported by the empirical literature. The coalition recommends increased communication with patients regarding fracture risk, mortality and morbidity outcomes, and fracture risk reduction. Risk assessment (including fall history) should occur at regular intervals with referral to physical and/or occupational therapy as appropriate. Oral, intravenous, and subcutaneous pharmacotherapies are efficacious and can reduce risk of future fracture. Patients need education, however, about the benefits and risks of both treatment and not receiving treatment. Oral bisphosphonates alendronate and risedronate are first-line options and are generally well tolerated; otherwise, intravenous zoledronic acid and subcutaneous denosumab can be considered. Anabolic agents are expensive but may be beneficial for selected patients at high risk. Optimal duration of pharmacotherapy is unknown but because the risk for second fractures is highest in the early post-fracture period, prompt treatment is recommended. Adequate dietary or supplemental vitamin D and calcium intake should be assured. Individuals being treated for osteoporosis should be reevaluated for fracture risk routinely, including via patient education about osteoporosis and fractures and monitoring for adverse treatment effects. Patients should be strongly encouraged to avoid tobacco, consume alcohol in moderation at most, and engage in regular exercise and fall prevention strategies. Finally, referral to endocrinologists or other osteoporosis specialists may be warranted for individuals who experience repeated fracture or bone loss and those with complicating comorbidities (eg, hyperparathyroidism, chronic kidney disease). © 2019 American Society for Bone and Mineral Research.

Clinical manifestations of osteoarthritis in osteoporotic and osteopenic postmenopausal women.

OBJECTIVE: We investigated the frequency of clinical manifestations of osteoarthritis in women with low BMD. METHODS: This prospective epidemiological study investigated the degree of osteoarthritic pain and functional disability in symptomatic joints of a randomly selected population of postmenopausal Greek women aged >45 years with osteoporosis or osteopenia. Degree of osteoarthritic impairment (none, mild, moderate or severe) was classified at the knee, hip, neck or hand using a site-specific internationally validated osteoarthritis questionnaire. RESULTS: 3000 women were included with mean age of 66.7 years. Osteoporosis was more common than osteopenia. Mild osteoarthritic impairment was most prevalent. An inverse relationship between severity of osteoarthritic impairment and mean femoral neck T-score was observed, regardless of site. There was a significant difference in mean femoral neck T-score between patients with severe osteoarthritic impairment and those with no, mild, or moderate impairment. This was also observed when lumbar spine BMD results were pooled. CONCLUSIONS: Most postmenopausal women with low BMD suffer from osteoarthritic impairment, with an inverse association between severity of osteoarthritic impairment and mean femoral neck T-score. Mean lumbar spine or femoral neck T-scores of patients with severe osteoarthritic impairment were significantly lower than those of patients with less impairment.

Assessment of the antiosteoporotic treatment initiation: A retrospective observational study in Greece.

OBJECTIVE: A study to retrospectively assess the decision to implement treatment for osteoporosis based on Greek version of FRAX tool. METHODS: The study population was 1000 postmenopausal women aged 45 or above, excluding those with medical conditions demanding specific osteoporosis management. Data were collected regarding their medical history and additionally, risk factors incorporated in FRAX questionnaire. FRAX score was estimated at the time of the anti-osteoporotic treatment initiation. RESULTS: The mean age of the study sample was 58.5±8.79 years. 46.8% of the participating osteopenic women had initiated treatment for osteoporosis at their first consultation while the 80.6% met the current national intervention threshold of FRAX tool. CONCLUSION: Stemming from our results there is an indication that women who are borderline eligible for treatment and seek consultation for osteoporosis are likely to be given treatment regardless of the potential benefit. One cannot ignore the fact that a clinician's good clinical judgment is of the utmost importance and under no circumstances can be replaced by any prognostic assessment tool.

Evaluation of commonly used nutritional assessment methods in hip fracture patients.

OBJECTIVE: Malnutrition is a common problem in hip fracture patients. The prevalence of malnutrition and available nutritional markers for use for nutritional assessment in this population group was investigated. METHODS: This is a case control study including 214 patients with a hip fracture from "KAT" Hospital in Athens, Greece, and 108 controls from three Elderly Open Protection Centers. Main outcome measures were anthropometric [Body Mass Index (BMI), triceps skinfold thickness (TST) and mid-arm muscle circumference (MAMC)] and biochemical parameters (serum albumin and serum cholesterol). Mini Nutritional Assessment (MNA) was used for malnutrition assessment. RESULTS: Based on MNA score only, we found 19.5 % vs. 0.9% malnourished, 54.6% vs. 32.4% at risk and 25.9% vs. 66.7% well-nourished, in hip fracture group and controls, respectively. All anthropometric parameters of malnutrition were significantly lower in the hip fracture patients compared to controls (p value<0.05). Serum albumin and serum-cholesterol levels correlated negatively significantly with s-CRP levels (R2=0.247, p<0.001 and R2=0.06, p<0.001, respectively) in the hip fracture group. CONCLUSIONS: Hip fracture patients are often malnourished. MNA application may be helpful in identifying malnourished hip fracture patients. Moreover, serum cholesterol may be a useful marker of malnutrition in hip fracture patients.

Evaluation of the first fracture liaison service in the Greek healthcare setting.

We evaluated the first implementation of FLS in the Greek healthcare setting, at the 251 Hellenic Air Force and VA General Hospital of Athens. Participation rate was moderate (54.5%) and needs improvement; osteoporosis medication was either suggested or reviewed in 74 out of the 116 patients recruited. PURPOSE: The purpose of this study was to evaluate the first implementation of a fracture liaison service (FLS) in Greece, at the 251 Hellenic Air Force and VA General Hospital, Athens. METHODS: Single-center, prospective study from May 1, 2013 to April 30, 2015 (first year-second year follow-up) was conducted. Patients of both genders aged 40-90 years old, with a history of a low trauma fracture and willing to participate, were included after identification by an FLS nurse. Following recruitment, osteoporosis risk factors were assessed, FRAX score was calculated for treatment-naïve patients, bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry (DXA), and osteoporosis treatment was suggested where applicable. The rate of participation, the indication of osteoporosis treatment, and the difficulties met were evaluated. RESULTS: Of the eligible 213 patients, 97 (45.5%) were reluctant to participate for personal reasons. From the 116 initially recruited patients (mean age 74.8 ± 12 years), 77 (66.4%) discontinued their participation at some point for various reasons and 39 patients concluded the study. All 116 patients were assessed for osteoporosis risk factors and given a tailor-made exercise and education program, while FRAX score was assessed in all treatment-naïve patients (74 patients, 63.8%). Osteoporosis medication was suggested or reviewed in 74 patients; however, an adherence rate of 100% is only available for the 24 who concluded the study. CONCLUSIONS: We report the first implementation of FLS in the Greek healthcare setting. The participation rate is moderate and definitely needs improvement.

Development and validation of an osteoporosis treatment questionnaire (OSTREQ) evaluating physicians' criteria in the choice of treatment.

OBJECTIVE: This article describes the development and validation of the osteoporosis treatment questionnaire (OSTREQ), which is a physician-reported outcome tool aiming to evaluate physicians' criteria in the choice of osteoporosis treatment. DESIGN: The questionnaire -named OSTREQ- consisting of 17 questions that were divided into eight sections "Health Care System", "Patients' Preference in administration routes", "Usage, Cost", "Severity of Disease", "Treatment Efficacy", "Safety Profile", "Pharmaceutical Industry", affecting the decision and overall execution of a therapeutic approach, was developed by an expert panel and was later officially translated into English. In the second phase, orthopedic surgeons were asked to complete OSTREQ. Six indirect methods to evaluate validity were adopted: exploratory factor analysis, confirmatory factor analysis, subscale validity, known group validity, floor or ceiling effects, interpretability. To assess the reliability of the questionnaire, internal consistency validity as well as test-retest and parallel forms were calculated. RESULTS: One hundred seventy-two orthopedic surgeons were interviewed with an average period of experience in clinical practice of 10.5 years (SD ±8.9 years). The factors "Severity of Disease" and "Treatment Efficacy" were the most important in the choice of osteoporosis treatment, while the factor "Pharmaceutical Industry" had the least impact. The methodology of validation proved that the questionnaire possesses construct validity, discriminate ability, reliability, and sensitivity to change. CONCLUSIONS: OSTREQ represents a comprehensive and focused tool that, for the first time, assesses physicians' criteria in the choice of osteoporosis treatment. This tool could assist health care systems and pharmaceutical companies to be aware which parameters drive physicians' preferences regarding osteoporosis treatment.

Analgesic effect of nasal salmon calcitonin during the early post-fracture period of the distal radius fracture.

OBJECTIVES: To investigate the analgesic effect of nasal salmon calcitonin on the post-fracture period of distal radius fracture. METHODS: In this prospective randomized double-blind study, forty-one postmenopausal women with a recent distal radius fracture treated conservatively were randomly assigned to receive either 200 IU of intranasal salmon calcitonin or placebo daily for 3 months following fracture. The assessment of the patient's pain was recorded using the Visual Analogue Scale (VAS). RESULTS: The average age of the calcitonin group was 67.11 (SD, ±8.68) years and 64.91 (SD, ±7.48) of the placebo group. In the calcitonin group, the mean VAS score improved from 4.05 to 0.53 while in the placebo group from 3.36 to 0.32. A higher decrease of VAS score during the first post-fracture period was observed in the calcitonin group. CONCLUSIONS: In the study, there is a statistically significant calcitonin mediated analgesic effect in the immediate post fracture period (at 10 days) when compared to placebo group. These results are in accordance with literature referring to the analgesic effect of calcitonin in the acute osteoporotic vertebral compression fracture. Thus calcitonin administration could be recommended to a short term course in acute osteoporotic conservatively treated distal radius fractures.