A randomized, double-blind study to compare the efficacy and safety of nalbuphine nasal spray and injectable solution in patients after orthopaedic interventions and traumatological procedures.

AIMS: Our previous 3-period crossover study in healthy volunteers comparing the pharmacokinetics of nalbuphine nasal spray Apain with parenteral nalbuphine solution demonstrated high bioavailability of the nasal spray and close similarity of pharmacokinetic profiles after intranasal and intramuscular administration, especially within 30 min postdose. The aim of the present study was a noninferiority assessment of nalbuphine nasal spray vs. intramuscular injection for pain relief in postoperative patients. METHODS: Ninety orthopaedic and traumatology patients were enrolled in this double-blind, randomized study of the effectiveness and tolerance of a single 10.5 mg dose of nalbuphine nasal spray vs. 10 mg intramuscular injection. The summed pain intensity difference (SPID0-6) calculated using visual analogue scale scores was the primary study endpoint. RESULTS: Of 90 subjects enrolled, the per-protocol efficacy population comprised 79 patients; 6 patients in the reference group and 5 patients in the test group were excluded due to remedication. The mean values of study endpoints with 95% confidence interval were as follows in reference and test groups, respectively: SPID0-6 = 228.08 (205.73-250.43) vs. 248.73 9 (225.83-271.63), time to pain relief onset = 0.28 h (0.25-0.31) vs. 0.27 h (0.25-0.29), duration of analgesia = 5.55 h (5.17-5.93) vs. 5.51 h (5.10-5.92), area under the curve = 119.30 (91.17-147.43) vs. 99.81 (74.52-107.10). No statistically significant differences were revealed. CONCLUSION: Nalbuphine nasal spray Apain has been proven to be a safe, noninvasive alternative to intramuscular nalbuphine to relieve severe postoperative pain. Designed for self-administration and dose-adjusting, the noncontrolled opioid analgesic nalbuphine spray can be used for patient-controlled analgesia in out-of-hospital, field and home settings.

Comparative study in vivo of the osseointegration of 3D-printed and plasma-coated titanium implants.

BACKGROUND: Total hip arthroplasty is a common surgical treatment for elderly patients with osteoporosis, particularly in postmenopausal women. In such cases, highly porous acetabular components are a favorable option in achieving osseointegration. However, further discussion is needed if use of such acetabular components is justified under the condition of normal bone mass. AIM: To determine the features of osseointegration of two different types of titanium implants [3-dimensional (3D)-printed and plasma-coated titanium implants] in bone tissue of a distal metaphysis in a rat femur model. METHODS: This study was performed on 20 white male laboratory rats weighing 300-350 g aged 6 mo. Rats were divided into two groups of 10 animals, which had two different types of implants were inserted into a hole defect (2 × 3 mm) in the distal metaphysis of the femur: Group I: 3D-printed titanium implant (highly porous); Group II: Plasma-coated titanium implant. After 45 and 90 d following surgery, the rats were sacrificed, and their implanted femurs were extracted for histological examination. The relative perimeter (%) of bone trabeculae [bone-implant contact (BIC%)] and bone marrow surrounding the titanium implants was measured. RESULTS: Trabecular bone tissue was formed on the 45th day after implantation around the implants regardless of their type. 45 d after surgery, group I (3D-printed titanium implant) and group II (plasma-coated titanium implant) did not differ in BIC% (83.51 ± 8.5 vs 84.12 ± 1 .73; P = 0.838). After 90 d, the BIC% was higher in group I (87.04 ± 6.99 vs 81.24 ± 7.62; P = 0.049), compared to group II. The relative perimeter of the bone marrow after 45 d did not differ between groups and was 16.49% ± 8.58% for group I, and 15.88% ± 1.73% for group II. Futhermore, after 90 d, in group I the relative perimeter of bone marrow was 1.4 times smaller (12.96 ± 6.99 vs 18.76 ± 7.62; P = 0.049) compared to the relative perimeter of bone marrow in group II. CONCLUSION: The use of a highly porous titanium implant, manufactured with 3D printing, for acetabular components provides increased osseointegration compared to a plasma-coated titanium implant.

PERIACETABULAR BONE CHANGES AFTER TOTAL HIP ARTHROPLASTY WITH HIGHLY POROUS TITANIUM CUPS IN PATIENTS WITH LOW BONE MASS.

OBJECTIVE: The aim: To assess the bone remodeling around highly porous titanium cups TTM in patients with low bone mass one year after total hip arthroplasty (THA). PATIENTS AND METHODS: Materials and methods: In this prospective study were included 18 patients (18 hips), whom was performed primary THA with the use of TTM cups. According to T-score of Lumbar Spine, patients were divided into 2 groups: normal bone mineral density (BMD) (n=9) if T-score ≥ -1, and low BMD (n=9) if T-score < -1. According to DeLee and Charnley's model BMD in 3 periacetabular regions were evaluated 1 week and 1 year after THA. RESULTS: Results: One year after primary THA, BMD of all 3 periacetabular regions did not differ in patients of both groups comparing with initial data. One week after THA, it was found that BMD R1 and BMD R3 in low BMD group were lower by 1.4 times (p=0.035) and 1.5 times (р=0.001) respectively, BMD R2 did not differ from the normal BMD group. One year after THA it was found that in low BMD group BMD R1 and BMD R2 were lower by 1.5 times (р=0.005) and 1.3 times (р=0.050) respectively, BMD R3 did not differ from the group with normal BMD. CONCLUSION: Conclusions: The use of highly porous titanium cups TTM in patients with low bone mass did not lead to a bone loss in DeLee and Charnley periacetabular zones one year after THA. Consequently, the use of these cups in patients with low bone mass undergoing THA is a valuable treatment option.

Osseointegration of porous titanium and tantalum implants in ovariectomized rabbits: A biomechanical study.

BACKGROUND: Today, biological fixation of uncemented press-fit acetabular components plays an important role in total hip arthroplasty. Long-term stable fixation of these implants depends on the osseointegration of the acetabular cup bone tissue into the acetabular cup implant, and their ability to withstand functional loads. AIM: To compare the strength of bone-implant osseointegration of four types of porous metal implants in normal and osteoporotic bone in rabbits. METHODS: The study was performed in 50 female California rabbits divided into non-ovariectomized (non-OVX) and ovariectomized groups (OVX) at 6 mo of age. Rabbits were sacrificed 8 wk after the implantation of four biomaterials [TTM, CONCELOC, Zimmer Biomet's Trabecular Metal (TANTALUM), and ATLANT] in a 5-mm diameter defect created in the left femur. A biomechanical evaluation of the femur was carried out by testing implant breakout force. The force was gradually increased until complete detachment of the implant from the bone occurred. RESULTS: The breakout force needed for implant detachment was significantly higher in the non-OVX group, compared with the OVX group for all implants (TANTALUM, 194.7 ± 6.1 N vs 181.3 ± 2.8 N; P = 0.005; CONCELOC, 190.8 ± 3.6 N vs 180.9 ± 6.6 N; P = 0.019; TTM, 186.3 ± 1.8 N vs 172.0 N ± 11.0 N; P = 0.043; and ATLANT, 104.9 ± 7.0 N vs 78.9 N ± 4.5 N; P = 0.001). In the OVX group, The breakout forces in TANTALUM, TTM, and CONCELOC did not differ significantly (P = 0.066). The breakout force for ATLANT in the OVX group was lower by a factor of 2.3 compared with TANTALUM and CONCELOC, and by 2.2 compared with TTM (P = 0.001). In the non-OVX group, the breakout force for ATLANT was significantly different from all other implants, with a reduction in fixation strength by a factor of 1.9 (P = 0.001). CONCLUSION: TANTALUM, TTM, and CONCELOC had equal bone-implant osseointegration in healthy and in osteoporotic bone. ATLANT had significantly decreased osseointegration (P = 0.001) in healthy and in osteoporotic bone.

Comparative analysis of osseointegration in various types of acetabular implant materials.

BACKGROUND: There is a lack of comparative data on osseointegration (BIC) of acetabular cup surfaces in hip arthroplasty in both normal bone mineral density and in conditions of osteoporosis. AIM: To compare osseointegration of acetabular implants with various types of surfaces in an animal model with normal and osteoporotic bone tissue. MATERIAL AND METHODS: The study was performed on 60 rats. To simulate osteoporosis ovariectomy was performed in 30 animals. Thirty healthy rats served as controls. In standardised defects of the distal metadiaphysis of the femur we implanted: porous tantalum Trabecular Metal (A), Trabecular Titanium (B), Titanium with Gription coating (C), Stiktite (D), and Tritanum (E). Bone apposition (osseointegration) was defined as all areas of direct "bone-to-implant contact" (BIC). RESULTS: No qualitative morphological differences in the evaluation of BIC around different implant types was seen in normal rats and rats with osteoporosis. Connective tissue areas around implants were larger in rats with osteoporosis. Morphometric studies showed that the highest BIC were seen in implants A and B, both in healthy animals ([72.00 ± 3.48]% and [67.46 ± 1.69]%) and ones with osteoporosis ([59.19 ± 2.10]% and [53.36 ± 2.57]%). BIC was (60.10 ± 2.05)%, (60.26 ± 2.36)%, and (61.78 ± 2.27)% around implants C, D and E in healthy rats, respectively. BIC in osteoporosis was (45.39 ± 2.37)%, (47.81 ± 2.41)% and (42.10 ± 1.44)%, respectively. CONCLUSION: Our study showed that the evaluated implants have good BIC features. Furthermore, based on histomorthometry and histology, Porous tantalum Trabecular Metal (A) and Trabecular Titanium (B) implants exhibit higher BIC with bone tissue.