Due to its high prevalence und sometimes serious medical consequences, osteoporosis is of highest socio-economic importance. Medical experts are confronted with it in a wide variety of fields of law. In order to be able to correctly classify the disease in the respective legal framework, current knowledge about it is required. Important classifications as well as scientifically determined findings on fractures and fracture healing are in the foreground. This knowledge can be used to answer questions concerning prevention, reduced earning capacity, incapacity for work, context assessments or restrictions according to the social compensation law or the severely disabled law.

Vitamin D plays a significant role in musculoskeletal health by regulating calcium, phosphate, and promoting new bone mineralization. The purpose of this study was to understand the effect of dietary vitamin D on general bone health during peri-operative bone healing via an in vivo dosing study of vitamin D in a rat posterolateral fusion model using autograft. Vitamin D Deficient (DD), vitamin D Insufficient (ID), Control vitamin D (CD), and Hyper-vitamin D (HD) groups were studied. Increasing dietary vitamin D improved quantitative measures of femoral geometry, including femoral strength, stiffness, and density. Femoral biomechanics, cortical thickness, moment of inertia, cross-sectional area, and measures from bone ashing were all greater in the HD group versus the CD. This suggests that additional dietary vitamin D above normal levels during spinal fusion may lead to improvement in bone health. Serum vitamin D levels were also observed to decrease during fusion healing. These results demonstrate that dietary vitamin D improves general bone health in the femur of a rat model during posterolateral spinal fusion. This suggests a role for further clinical evaluation of vitamin D dietary intake during the peri-operative period, with the possibility of avoiding adverse consequences to general bone health. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1435-1443, 2018.

An in vivo dosing study of vitamin D in a rat posterolateral spinal fusion model with autogenous bone grafting. Rats randomized to 4 levels of vitamin D-adjusted rat chow, longitudinal serum validation, surgeons/observers blinded to dietary conditions, and rats followed prospectively for fusion endpoint.

To assess the impact of dietary and serum levels of vitamin D on fusion success, consolidation of fusion mass, and biomechanical stiffness after posterolateral spinal fusion procedure.

Metabolic risk factors, including vitamin D insufficiency, are often overlooked by spine surgeons. Currently, there are no published data on the causal effect of insufficient or deficient vitamin D levels on the success of establishing solid bony union after a spinal fusion procedure.

Fifty rats were randomized to 4 experimentally controlled rat chow diets: normal control, vitamin D-deficient, vitamin D-insufficient, and a nontoxic high dose of vitamin D, 4 weeks prior to surgery and maintained postsurgery until sacrifice. Serum levels of 25(OH)D were determined at surgery and sacrifice using radioimmunoassay. Posterolateral fusion surgery with tail autograft was performed. Rats were sacrificed 12 weeks postoperatively, and fusion was evaluated via manual palpation, high-resolution radiographs, micro-computed tomographic scans, and biomechanical testing.

Serum 25(OH)D and calcium levels were significantly correlated with vitamin D-adjusted chow (P < 0.001). There was a dose-dependent relationship between vitamin D-adjusted chow and manual palpation fusion, with greatest differences found in measures of radiographical density between high and deficient vitamin D (P < 0.05). Adequate levels of vitamin D (high and normal control) yielded stiffer fusion than inadequate levels (insufficient and deficient) (P < 0.05).

Manual palpation fusion rates increased with supplementation of dietary vitamin D. Biomechanical stiffness, bone volume, and density were also positively related to vitamin D and calcium.

N/A.

In order to assess the effect of osteoporosis on healing time, the files of 165 patients with femoral shaft fractures that were treated in our institution with locked-reamed intramedullary nailing were retrospectively reviewed.

Patients with open fractures, pathological fractures, revision surgery, severe brain injuries and prolonged ITU stay were excluded. In all patients the Singh-index score for osteoporosis and the canal bone ratio (CBR) were assigned. Sixty-six patients fulfilled the inclusion criteria. Patients were divided into two groups; group A (29 patients) consisted of patients over 65 years old with radiological evidence of osteoporosis and group B (37 patients) of patients between 18 and 40 years old with no signs of osteoporosis.

In all group A patients Singh score < or =4 and CBR>0.50 were assigned, suggesting the presence of osteoporosis, whereas all group B patients were assigned with Singh score > or =5 and CBR<0.48. Fractures of group A healed in 19.38+/-5.9 weeks (12-30) and in group B 16.19+/-5.07 weeks (10-28), P=0.02.

Fracture healing of nailed femoral diaphyseal fractures is significantly delayed in older osteoporotic patients. Further studies are required to clarify the exact impact of osteoporosis in the whole healing process.

A new class of parathyroid hormone-related protein (PTHrP) analogs has been developed that causes a rapid gain in both trabecular and cortical bone in models of osteopenia. This study investigates the efficacy of the PTHrP analog, RS-66271 ([MAP(1-10)]22-31 hPTHrP(1-34)-NH(2)), as systemic therapy for impaired bone healing in corticosteroid-treated rabbits. A 1 mm defect was created bilaterally in the ulnae of 30 rabbits. Delayed healing was induced by daily injections of prednisone (0.15 mg/kg) beginning 2 months prior to surgery and continuing until killing. Rabbits in the experimental group received daily subcutaneous injections of PTHrP analog RS-66271 (0.01 mg/kg) starting 1 day after surgery. Control animals received subcutaneous normal saline. At the 6 week timepoint, nine of ten ulnae from PTHrP-treated rabbits achieved radiographic union, whereas only two of ten limbs achieved union in control rabbits (p < 0.01). In a separate part of the study, 20 animals (10 control, 10 RS-66271-treated) were killed when radiographic union was achieved bilaterally. In this portion of the study, all limbs in animals treated with PTHrP achieved union by 6 weeks. In the control animals that were allowed to heal for 10 weeks, only 20% of the limbs achieved radiographic union. In addition, ulnae in the PTHrP-analog-treated rabbits showed greater radiographic intensity (20%-40%), larger callus area (209% anteroposterior view, 417% lateral view) (mean area on AP radiographs: control, = 387 +/- 276 mm(2); PTHrP analog, 1195 +/- 408 mm(2)), and greater stiffness (64%) and torque (87%) when compared with controls. RS-66271 was shown to be an effective therapy for preventing impaired bone healing caused by prednisone in a rabbit model.

It has been shown that low-intensity pulsed ultrasound (US) accelerates fracture healing in animal models and in clinical studies. However, the mechanism by which US accelerates fracture healing remains unclear. Systemic factors and several growth factors, such as platelet-derived growth factor (PDGF), are thought to be involved in the process of fracture healing. In the present study, we examined the effects of US and 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] on growth factor secretion in a co-culture system of human osteoblastic cells (SaOS-2) and endothelial cells (HUVEC). US was applied to cultured cells for 20 min daily for four consecutive days. US treatment increased the PDGF-AB level in the conditioned media. 1,25-(OH)2D3 (1 x 10(-8) M) also enhanced PDGF-AB secretion. The secretion of PDGF-AB was synergistically increased by the combination of US and 1,25-(OH)2D3. These results suggest that the stimulation of growth factor secretion from cells by US and 1,25-(OH)2D3 treatment may be involved in the acceleration of fracture healing.

Using a rat fracture model, we investigated the effects of a decrease in serum levels of thyroid hormone on the fracture-repair process. Rats were divided into the following groups: (a) controls, (b) those treated with methimazole for the duration of the experiment, and (c) those treated with methimazole and L-thyroxine, receiving both for the same duration. Three weeks after the initiation of pharmacologic treatment, closed femoral fractures were produced. The formation of cartilage tissue in the fracture callus in all rats was not obviously different on day 7 after fracture. In the rats treated with methimazole, differentiation from proliferating to hypertrophic chondrocytes in the fracture callus was less advanced and vascular invasion was clearly inhibited on day 12. Gene expression of alkaline phosphatase and osteocalcin in the callus was significantly lower in these rats than in the controls on days 10, 12, and 14. The mechanical properties of the fracture callus were also significantly weaker in these animals than in the controls on day 21, resulting in impaired fracture repair. These results demonstrate that hypothyroidism inhibits endochondral ossification, resulting in an impaired fracture-repair process. L-thyroxine replacement in the rats treated with methimazole caused the impaired repair process to revert to normal. These results indicate that thyroid hormone is one of the critical systemic factors for fracture repair.

The influence of intermittent parathyroid hormone (PTH(1-34)) administration on callus formation and mechanical strength of tibial fractures in rats was investigated after 20 and 40 days of healing. A dose of 60 microg of PTH(1-34)/kg/day and 200 microg of PTH(1-34)/kg/day, respectively, was administered during the entire periods of healing, and control animals with fractures were given vehicle. The dose of 200 microg of PTH(1-34)/kg/day increased the ultimate load and the external callus volume of the fractures by 75% and 99%, respectively, after 20 days of healing and by 175% and 72%, respectively, after 40 days of healing. The dose of 60 microg of PTH(1-34)/kg/day did not influence either ultimate load or external callus volume of the fractures after 20 days of healing, but the ultimate load was increased by 132% and the external callus volume was increased by 42% after 40 days of healing. During the healing period, the callus bone mineral content (BMC) increased in all groups. After 40 days of healing, the callus BMC was increased by 108% in the 200 microg of PTH(1-34)/kg/day group and by 76% in the 60 microg of PTH(1-34)/kg/day group. Both doses of PTH(1-34) steadily augmented the contralateral intact tibia BMC (20 days and 40 days: 60 microg of PTH (1-34)/kg/day 9% and 19%, respectively; 200 microg of PTH (1-34)/kg/day 12% and 27%, respectively) and bone mineral density (20 days and 40 days: 60 microg of PTH(1-34)/kg/day 11% and 12%, respectively; 200 microg of PTH(1-34)/kg/day 11% and 15%, respectively).

The incorporation of calcium, phosphate, and zinc into the callus of closed tibial fractures was studied in adult rats fed a standard diet. Low doses (60 ng/kg per day) of 1,25(OH)2D3 5 days a week greatly increased early callus mineralization. This was not related to an increased serum calcium-phosphate molar product but rather to a decreased ratio. The incorporation of zinc into callus seemed to be correlated to the mineralization process but not to the 1,25(OH)2D3 administration as such. The question of a direct, indirect, or a complex role of 1,25(OH)2D3 in bone formation and mineralization is discussed.