Dual-energy X-ray absorptiometry (DEXA) is increasingly used to measure changes in bone mineral density (BMD) around femoral prostheses after total hip arthroplasty. We have studied the factors which affect the accuracy of these measurements. The coefficient of variation was < 2% using a hydroxyapatite phantom, 2.7% in an anthropomorphic phantom specimen, and < 1% in repeated measurements on implanted cadaver femora. The precision did not vary with different implant materials or designs. In patients we found a mean precision error of 2.7% to 3.4%. The most significant factor affecting reproducibility was rotation of the femur. We conclude that DEXA is a precise method of measurement for small changes in BMD around femoral implants, but that correct and careful positioning of patients is essential to obtain reliable results

We describe the clinical and radiological outcome of 100 consecutive total hip replacements in 86 patients using the JRI Furlong hydroxyapatite-coated femoral component. The follow-up was 100% at a mean of ten years (9.0 to 12.0). All 54 living patients (62 hips) were examined annually. Their mean Merle d’Aubigné score was 5.8/5.6/4.6. A total of 32 patients had died. Their notes at the last annual assessment recorded a similar outcome to that of the living patients. Radiographs showed no radiolucent lines around any femoral component and there were no signs of impending failure. One patient required excision arthroplasty, but the femoral component had been bonded satisfactorily. There have been no other revisions of femoral components. Our findings suggest that the hydroxyapatite coating gives a satisfactory prosthesis-bone interface which is preferable to any other system

Implants of solid sintered hydroxyapatite form very tight bonds with living bone, but are susceptible to fatigue failure. This problem can be overcome by using plasma-sprayed apatite coatings on titanium implants. A very strong bond is formed between bone and this composite material; this was studied in canine bone with plug implants, avoiding any mechanical retention. Mechanical testing showed an interface shear strength at six weeks of 49 MPa with a maximum of 64 MPa after six months. There was histological evidence of direct bonding between the apatite coating and living bone while uncoated control plugs were easily extracted. The results indicate that apatite-coated implants can form a chemical fixation with a strength comparable to that of cortical bone itself. This fixation is far stronger than that provided by current cemented or uncemented fixation techniques

Quantitative polarised light microscopy was applied to sections of unfixed, undecalcified bone taken at operation from patients with two types of proximal femoral fracture, subcapital and trochanteric. Specimens were also taken from the equivalent sites in otherwise normal subjects at autopsy, and from various other sites of traumatic fractures; these two latter groups acted as controls. Analysis of the 57 specimens disclosed changes in the nature of the bone at the site of subcapital fractures, namely the presence of relatively large crystals of hydroxyapatite and a change in the molecular orientation, but not total content, of the acidic proteoglycans of the bone matrix. Our results have confirmed and extended the findings of others on subcapital fractures, and have also shown very similar changes in the trochanteric fractures. It thus appears that the bony changes in the two types of proximal femoral fracture are not as different as has been suggested

Experimentally produced fractures in long bones studied by light and electron microscopic histochemistry were found to heal by a process of enchondral calcification. There was intense proliferation in the cells of the cambium layer of the periosteum, with differentiation to chondroblasts and osteoblasts, suggesting that this layer was the primary tissue responsible for development of the callus. Cytoplasmic processes of the hypertrophic chondrocytes appeared to bud and produce matrix vesicles. Alkaline phosphatase activity was detected along the plasma membrane of the hypertrophic chondrocytes and around the matrix vesicles, before any signs of mineral deposition. Calcification took place by deposition of hydroxyapatite crystals in and around these matrix vesicles which frequently showed alkaline phosphatase activity. It is suggested that there is a close functional association between alkaline phosphatase activity and calcification in the process of fracture healing, which is another type of enchondral calcification mediated by matrix vesicles

We studied the pattern of . 99m. Tc-methylene diphosphonate uptake around uncemented femoral components in 44 asymptomatic hip arthroplasties, performing isotope scans at intervals from 4 to 48 months after operation. We used phase-III images obtained with a high-resolution gamma camera and measured the activity in various zones using a specially designed computer program. The components studied at 4, 6, 9 and 12 months were coated with hydroxyapatite (HA) and those studied at 18, 24, 36 and 48 months were not coated. We found a statistically significant fall in activity between four and six months around HA-coated prostheses in all five femoral periprosthetic zones. After six months activity was relatively uniform, but remained higher than that in normal femoral bone at 48 months in non-coated prostheses. We discuss the application of these patterns in the evaluation of painful cementless hip arthroplasties

Pin loosening and infection are inherent complications of external fixation. This study deals with their effects of using either hydroxyapatite (HA)-coated or uncoated external fixation pins in leg-lengthening procedures on patients of short stature. We used HA-coated pins on one side and uncoated pins on the other (randomly determined) in 28 bilateral lengthenings undertaken in 23 patients. A total of 322 pins was used. The mean implantation time was 530 days and the mean lengthening achieved was 78% of initial bone length. Mean extraction torque was 7611.6 Nmm degree. −1. for HA-coated and 85.4 Nmm degree. −1. for uncoated pins (p < 0.001). The rate of pin loosening was 4% (7/ 161) for HA-coated and 80% (129/161) for uncoated pins (p < 0.001). There was no statistically significant difference in the incidence of pin-track infection between the two groups. The use of HA coating appears to be an effective method of reducing the incidence of pin loosening in external fixation with a long implantation time and for mechanically highly stressed procedures such as leg lengthening for short stature

We performed a histological and histomorphometric examination in five cadaver specimens of the femoral and acetabular components and the associated tissue which had been recovered between 3.3 and 6.2 years after primary total hip arthroplasty (THA) using a proximal hydroxyapatite (HA)-coated titanium alloy implant. All had functioned well during the patients’ life. All the stems were fixed in the femur and showed osseointegration of both the proximal and distal parts. The amount of residual HA was greatest in the distal metaphyseal sections, indicating that the rate of bone remodelling may be the main factor causing loss of HA. The level of activity of the patient was the only clinical factor which correlated with loss of coating. The percentage of bone-implant osseointegration was almost constant, regardless of the amount of HA residue, periprosthetic bone density or the time of implantation. HA debris was seldom observed and if present did not cause any adverse or inflammatory reaction. Partial debonding did occur in one case as a result of a polyethylene-induced inflammatory reaction

Aims

CERAMENT|G is an absorbable gentamicin-loaded biocomposite used as an on-site vehicle of antimicrobials for the treatment of chronic osteomyelitis. The purpose of the present study was to investigate the sole effect of CERAMENT|G, i.e. without additional systemic antimicrobial therapy, in relation to a limited or extensive debridement of osteomyelitis lesions in a porcine model.

We have compared the survival of two hydroxyapatite (HA)-coated cups, 1208 Atoll hemispheric and 2641 Tropic threaded, with cemented Charnley all-polyethylene cups (16 021) using the Cox regression model. The Tropic cup used in combination with an alumina ceramic femoral head, had good results, similar to those of the Charnley cup. When used in combination with a stainless-steel head, however, the risk of revision beyond four years was increased 3.4 times for the Tropic cup compared with the Charnley cup (p < 0.001). Over the same period, the Atoll cup had an increased risk of revision of 3.8 times when used with the alumina heads (p < 0.001) and an increased risk of 6.1 times when used with stainless-steel heads (p < 0.001). Revision because of wear and osteolysis was more common with both types of HA-coated cup than with the Charnley cup. The rate of revision of the Atoll cup because of aseptic loosening was also increased. We found that HA-coated cups did not perform better than the Charnley cup

We have developed a new drug delivery system using porous apatite-wollastonite glass ceramic (A-W GC) to treat osteomyelitis. A-W GC (porosity, 70% and 20% to 30%), or porous hydroxyapatite (HA) blocks (porosity 35% to 48%) used as controls, were soaked in mixtures of two antibiotics, isepamicin sulphate (ISP) and cefmetazole (CMZ) under high vacuum. We evaluated the release concentrations of the antibiotics from the blocks. The bactericidal concentration of ISP from A-W GC was maintained for more than 42 days, but that from HA decreased to below the detection limit after 28 days. The concentrations of CMZ from both materials were lower than those of ISP. An in vivo study using rabbit femora showed that an osseous concentration of ISP was maintained at eight weeks after implantation. Osteoconduction of the A-W GC block was good. Four patients with infected hip arthroplasties and one with osteomyelitis of the tibia have been treated with the new delivery system with excellent results

We have carried out a prospective, randomised study designed to compare the long-term stability of the stem of cementless femoral implants with differing surface configurations. A total of 50 hips (46 patients) was randomised into two groups, according to whether the medullary stem had been grit blasted (GB) or coated with hydroxyapatite (HA). Both femoral prostheses were of the same geometrical design. We used Ein Bild Roentgen Analyse femoral component analysis (EBRA-FCA) to assess the stability of the stem. The mean follow-up was for 8.66 years. The mean migration of the stem was 1.26 mm in the HA group compared with 2.57 mm in the GB group (Mann-Whitney U test, p = 0.04). A mixed model ANOVA showed that the development of subsidence was statistically different in the two groups during the first 24 months. After this subsidence increased in both groups with no difference between them. Our results indicate that, with the same design of stem, HA coating enhanced the stability of the femoral stem when compared with GB stems

Ten acetabular cups coated with hydroxyapatite (HA) had originally been inserted in five primary and five revision total hip replacements. The thickness of the HA was 155 ± 35 μm. The cups, which were well-fixed, were retrieved, with their adherent tissue, at reoperation after 0.3 to 5.8 years because of infection (five hips), wear of polyethylene (three hips), and instability (two hips). Undecalcified sections showed a direct contact between bone and osteoid-like tissue which had formed directly onto the HA coating. The area within the threads and their mirror images, as well as the implant-tissue interfaces consisted of similar amounts of bone and soft tissue. Degradation of HA was seen in all hips. The mean thickness of the remaining HA coating was 97 μm (95% CI 94 to 101). The metal interface comprised 66% HA. The HA-tissue interface contained more bone than soft tissue (p = 0.001), whereas the metal-tissue interface included more soft tissue than bone (p = 0.019). Soft tissue at the implant interface and poor replacement of HA by bone may interfere with long-term fixation

Between March 1990 and May 1991 we performed 85 primary total hip replacements in 74 patients using the Landos Atoll hydroxyapatite (HA)-coated cup and the Corail HA-coated stem. The patients were followed up for a mean of ten years. Of the 85 cups, 26 (31%) have already been revised and a further six are radiologically unstable and awaiting revision. Two femoral stems have been revised for infection without loosening. The retrieved acetabular cups were studied by SEM and image-processing techniques to quantify the amount of residual HA on the cup. This was correlated with the clinical variables and modes of failure. The residual HA (as a percentage of the surface) on the loose cups correlated negatively with the duration of implantation (r = −0.732, p < 0.001). Six cups were stable at revision and had more residual HA coating than those which were loose (p < 0.01). The rate of failure of the Landos Atoll HA-coated, smooth hemispherical cup with screw fixation is unacceptably high. Resorption of the HA coating is markedly increased in loose cups compared with stable cups. HA coating cannot substitute for stable mechanical fixation

We present the 5.6- to 7.6-year results of our first 118 hydroxyapatite (HA)-coated total hip replacements in patients under 66 years of age. The titanium femoral component has proximal HA coating and was usually articulated with an HA-coated threaded cup. The HA coating of 50 microns thickness has a porosity of below 3%, 97% HA purity and 65% crystallinity. The survival rate at a mean of six years was 100% for the HA-coated stems and 99% for the HA-threaded cups. The average Harris hip score at one year was 96, and at three years and thereafter 98. There was a very low incidence of early pain after surgery. Serial radiographs showed rapid bony integration of implants with evidence of bone apposition on the coating within six months. By Engh's criteria, all the femoral components had confirmed bone ongrowth after three years. We found no deterioration of results with time, and consider that our clinical and radiological results show that HA coatings can provide early pain relief and durable implant fixation

During the last decades, several research groups have used bisphosphonates for local application to counteract secondary bone resorption after bone grafting, to improve implant fixation or to control bone resorption caused by bone morphogenetic proteins (BMPs). We focused on zoledronate (a bisphosphonate) due to its greater antiresorptive potential over other bisphosphonates. Recently, it has become obvious that the carrier is of importance to modulate the concentration and elution profile of the zoledronic acid locally. Incorporating one fifth of the recommended systemic dose of zoledronate with different apatite matrices and types of bone defects has been shown to enhance bone regeneration significantly in vivo. We expect the local delivery of zoledronate to overcome the limitations and side effects associated with systemic usage; however, we need to know more about the bioavailability and the biological effects. The local use of BMP-2 and zoledronate as a combination has a proven additional effect on bone regeneration. This review focuses primarily on the local use of zoledronate alone, or in combination with bone anabolic factors, in various preclinical models mimicking different orthopaedic conditions.

Cite this article: I. Qayoom, D. B. Raina, A. Širka, Š. Tarasevičius, M. Tägil, A. Kumar, L. Lidgren. Anabolic and antiresorptive actions of locally delivered bisphosphonates for bone repair: A review. Bone Joint Res 2018;7:548–560. DOI: 10.1302/2046-3758.710.BJR-2018-0015.R2.

Aims

The aim of this study was to estimate the 90-day risk of revision for periprosthetic femoral fracture associated with design features of cementless femoral stems, and to investigate the effect of a collar on this risk using a biomechanical in vitro model.

We performed a retrospective analysis of the clinical and radiological outcomes of total hip replacement using an uncemented femoral component proximally coated with hydroxyapatite. Of 136 patients, 118 who had undergone 124 primary total hip replacements were available for study. Their mean age was 66.5 years (19 to 90) and the mean follow-up was 5.6 years (4.25 to 7.25). At the final follow-up the mean Harris hip score was 92 (47.7 to 100). Periprosthetic femoral fractures, which occurred in seven patients (5.6%), were treated by osteosynthesis in six and conservatively in one. We had to revise five femoral components, one because of aseptic loosening, one because of septic loosening and three because of periprosthetic fracture. At the final follow-up there were definite signs of aseptic loosening in two patients. Radiologically, proximal femoral bone loss in Gruen zones I and VI was evident in 96.8% of hips, while bone hypertrophy in zones III and V was seen in 64.7%. In 24 hips (20.2%) the mean subsidence of the stem was 3.7 mm which occurred within the first 12 postoperative weeks. This indicated poor initial stability, which might have been aggravated by early weight-bearing. The high rate of failure in our study suggests that proximal femoral bone loss affects the long-term survival of the replacement

We compared the radiological appearances and survival of four methods of fixation of a femoral stem in 538 hips after follow-up for five or ten years. The fixation groups were: 1) press-fit shot-blasted smooth Ti-Al-V stem; 2) press-fit shot-blasted proximally ridged stem; 3) proximal hydroxyapatite (HA) coating; and 4) cementing. Survival analysis at five to ten years showed better results in the HA-coated (100% at five to six years) and cemented stems (100% at 5 to 6 years) than in the two press-fit groups. There was a higher mean rate of migration in the smooth and ridged Ti-Al-V shot-blasted press-fit groups (0.8 mm/year and 0.6 mm/year, respectively) when compared with the HA-coated and cemented prostheses (both 0.3 mm/year). More radiolucent lines and osteolytic lesions were seen in the press-fit groups than in either the HA-coated or cemented implants, with a trend for a lower incidence of both in the HA compared with the cemented group. Proximal osteopenia increased in the press-fit and cemented prostheses with time, but did not do so in the HA group. There was a higher incidence of resorption of the femoral neck with time in the cemented group than in the other three. We conclude that the HA and the cemented interfaces both provide secure fixation with a trend in favour of HA. The cemented prosthesis meets the suggested National Institutes of Health definition of ‘efficacious’ at ten years