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The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 6 | Pages 760 - 768
1 Jun 2011
ten Broeke RHM Alves A Baumann A Arts JJC Geesink RGT

Four uncemented Symax hip stems were extracted at three weeks and nine, 13 and 32 months, respectively, for reasons other than loosening. The reasons for implant removal were infection in two cases, recurrent dislocation in one and acetabular fracture in one. They were analysed to assess the effect and behaviour of an electrochemically deposited, completely resorbable biomimetic BONIT-hydroxyapatite (HA) coating (proximal part) and a DOTIZE surface treatment (distal part) using qualitative histology, quantitative histomorphometry and scanning electron microscopy (SEM). Early and direct bone-implant bonding with signs of active remodelling of bone and the HA coating were demonstrated by histology and SEM. No loose BONIT-HA particles or delamination of the coating were observed, and there was no inflammation or fibrous interposition at the interface.

Histomorphometry showed bone-implant contact varying between 26.5% at three weeks and 83.5% at 13 months at the HA-coated implant surface. The bone density in the area of investigation was between 24.6% at three weeks and 41.1% at 32 months. The DOTIZE surface treatment of the distal part of the stem completely prevented tissue and bone apposition in all cases, thereby optimising proximal stress transfer.

The overall features of this implant, in terms of geometry and surface texture, suggest a mechanically stable design with a highly active biomimetic coating, resulting in rapid and extensive osseo-integration, exclusively in the metaphyseal part of the stem. Early remodelling of the HA coating does not seem to have a detrimental effect on short-term bone-implant coupling. There were no adverse effects identified from either the BONIT-HA coating or the DOTIZE surface treatment.


The Journal of Bone & Joint Surgery British Volume
Vol. 86-B, Issue 8 | Pages 1118 - 1123
1 Nov 2004
Singh S Trikha SP Edge AJ

We describe the clinical and radiological results of 38 total hip replacements (THR) using the JRI Furlong hydroxyapatite-ceramic (HAC)-coated femoral component in patients younger than 50 years. The mean age at the time of operation was 42 years (22 to 49) and the mean length of follow-up was ten years (63 to 170 months). All patients receiving a Furlong HAC THR were entered into the study regardless of the primary pathology including patients who had undergone previous hip surgery.

The mean Harris hip score improved from 44 before operation to 92 at the last postoperative review. After 12 years the cumulative surivival for the stem was 100% (95% confidence interval 89 to 100). No femoral component was revised. Our results show that the Furlong HAC implant gives excellent long-term results in young patients with high demands.


The Journal of Bone & Joint Surgery British Volume
Vol. 79-B, Issue 6 | Pages 1044 - 1044
1 Nov 1997
Fulford P


The Journal of Bone & Joint Surgery British Volume
Vol. 81-B, Issue 2 | Pages 368 - 369
1 Mar 1999
NELISSEN RGHH VALSTAR ER ROZING PM


The Journal of Bone & Joint Surgery British Volume
Vol. 80-B, Issue 4 | Pages 745 - 745
1 Jul 1998
BAUER TW


The Journal of Bone & Joint Surgery British Volume
Vol. 80-B, Issue 4 | Pages 745 - 746
1 Jul 1998
FURLONG R


The Journal of Bone & Joint Surgery British Volume
Vol. 80-B, Issue 2 | Pages 267 - 272
1 Mar 1998
Morscher EW Hefti A Aebi U

One concern about the fixation of HA-coated implants is the possible disintegration of the surface, with the migration of HA granules into the joint space, producing third-body wear.

We report a study of six revisions of HA-coated polyethylene RM cups at 9 to 14 years after successful primary arthroplasty. In all six hips, we found HA granules embedded in the articulating surface of the polyethylene, with abrasive wear of the cup and the metal femoral head. The cup had loosened in four hips and three showed severe osteolysis of the proximal femur.

Third-body wear due to HA particles from implant coating may produce severe clinical problems with few early warning signs. Further clinical, radiological and histological observations are needed to determine the possible incidence of this late complication in the various types of coating of a variety of substrates.


Bone & Joint Research
Vol. 12, Issue 7 | Pages 412 - 422
4 Jul 2023
Ferguson J Bourget-Murray J Hotchen AJ Stubbs D McNally M

Aims. Dead-space management, following dead bone resection, is an important element of successful chronic osteomyelitis treatment. This study compared two different biodegradable antibiotic carriers used for dead-space management, and reviewed clinical and radiological outcomes. All cases underwent single-stage surgery and had a minimum one-year follow-up. Methods. A total of 179 patients received preformed calcium sulphate pellets containing 4% tobramycin (Group OT), and 180 patients had an injectable calcium sulphate/nanocrystalline hydroxyapatite ceramic containing gentamicin (Group CG). Outcome measures were infection recurrence, wound leakage, and subsequent fracture involving the treated segment. Bone-void filling was assessed radiologically at a minimum of six months post-surgery. Results. The median follow-up was 4.6 years (interquartile range (IQR) 3.2 to 5.4; range 1.3 to 10.5) in Group OT compared to 4.9 years (IQR 2.1 to 6.0; range 1.0 to 8.3) in Group CG. The groups had similar defect sizes following excision (both mean 10.9 cm. 3. (1 to 30)). Infection recurrence was higher in Group OT (20/179 (11.2%) vs 8/180 (4.4%), p = 0.019) than Group CG, as was early wound leakage (33/179 (18.4%) vs 18/180 (10.0%), p = 0.024) and subsequent fracture (11/179 (6.1%) vs 1.7% (3/180), p = 0.032). Group OT cases had an odds ratio 2.9-times higher of developing any one of these complications, compared to Group CG (95% confidence interval 1.74 to 4.81, p < 0.001). The mean bone-void healing in Group CG was better than in Group OT, in those with ≥ six-month radiological follow-up (73.9% vs 40.0%, p < 0.001). Conclusion. Local antibiotic carrier choice affects outcome in chronic osteomyelitis surgery. A biphasic injectable carrier with a slower dissolution time was associated with better radiological and clinical outcomes compared to a preformed calcium sulphate pellet carrier. Cite this article: Bone Joint Res 2023;12(7):412–422


Bone & Joint Research
Vol. 9, Issue 10 | Pages 709 - 718
1 Oct 2020
Raina DB Liu Y Jacobson OLP Tanner KE Tägil M Lidgren L

Bone is a dynamic tissue with a quarter of the trabecular and a fifth of the cortical bone being replaced continuously each year in a complex process that continues throughout an individual’s lifetime. Bone has an important role in homeostasis of minerals with non-stoichiometric hydroxyapatite bone mineral forming the inorganic phase of bone. Due to its crystal structure and chemistry, hydroxyapatite (HA) and related apatites have a remarkable ability to bind molecules. This review article describes the accretion of trace elements in bone mineral giving a historical perspective. Implanted HA particles of synthetic origin have proved to be an efficient recruiting moiety for systemically circulating drugs which can locally biomodulate the material and lead to a therapeutic effect. Bone mineral and apatite however also act as a waste dump for trace elements and drugs, which significantly affects the environment and human health. Cite this article: Bone Joint Res 2020;9(10):709–718


Bone & Joint Research
Vol. 10, Issue 10 | Pages 677 - 689
1 Oct 2021
Tamaddon M Blunn G Xu W Alemán Domínguez ME Monzón M Donaldson J Skinner J Arnett TR Wang L Liu C

Aims. Minimally manipulated cells, such as autologous bone marrow concentrates (BMC), have been investigated in orthopaedics as both a primary therapeutic and augmentation to existing restoration procedures. However, the efficacy of BMC in combination with tissue engineering is still unclear. In this study, we aimed to determine whether the addition of BMC to an osteochondral scaffold is safe and can improve the repair of large osteochondral defects when compared to the scaffold alone. Methods. The ovine femoral condyle model was used. Bone marrow was aspirated, concentrated, and used intraoperatively with a collagen/hydroxyapatite scaffold to fill the osteochondral defects (n = 6). Tissue regeneration was then assessed versus the scaffold-only group (n = 6). Histological staining of cartilage with alcian blue and safranin-O, changes in chondrogenic gene expression, microCT, peripheral quantitative CT (pQCT), and force-plate gait analyses were performed. Lymph nodes and blood were analyzed for safety. Results. The results six months postoperatively showed that there were no significant differences in bone regrowth and mineral density between BMC-treated animals and controls. A significant upregulation of messenger RNA (mRNA) for types I and II collagens in the BMC group was observed, but there were no differences in the formation of hyaline-like cartilage between the groups. A trend towards reduced sulphated glycosaminoglycans (sGAG) breakdown was detected in the BMC group but this was not statistically significant. Functional weightbearing was not affected by the inclusion of BMC. Conclusion. Our results indicated that the addition of BMC to scaffold is safe and has some potentially beneficial effects on osteochondral-tissue regeneration, but not on the functional endpoint of orthopaedic interest. Cite this article: Bone Joint Res 2021;10(10):677–689


The Bone & Joint Journal
Vol. 103-B, Issue 3 | Pages 522 - 529
1 Mar 2021
Nichol T Callaghan J Townsend R Stockley I Hatton PV Le Maitre C Smith TJ Akid R

Aims. The aim of this study was to develop a single-layer hybrid organic-inorganic sol-gel coating that is capable of a controlled antibiotic release for cementless hydroxyapatite (HA)-coated titanium orthopaedic prostheses. Methods. Coatings containing gentamicin at a concentration of 1.25% weight/volume (wt/vol), similar to that found in commercially available antibiotic-loaded bone cement, were prepared and tested in the laboratory for: kinetics of antibiotic release; activity against planktonic and biofilm bacterial cultures; biocompatibility with cultured mammalian cells; and physical bonding to the material (n = 3 in all tests). The sol-gel coatings and controls were then tested in vivo in a small animal healing model (four materials tested; n = 6 per material), and applied to the surface of commercially pure HA-coated titanium rods. Results. The coating released gentamicin at > 10 × minimum inhibitory concentration (MIC) for sensitive staphylococcal strains within one hour thereby potentially giving effective prophylaxis for arthroplasty surgery, and showed > 99% elution of the antibiotic within the coating after 48 hours. There was total eradication of both planktonic bacteria and established bacterial biofilms of a panel of clinically relevant staphylococci. Mesenchymal stem cells adhered to the coated surfaces and differentiated towards osteoblasts, depositing calcium and expressing the bone marker protein, osteopontin. In the in vivo small animal bone healing model, the antibiotic sol-gel coated titanium (Ti)/HA rod led to osseointegration equivalent to that of the conventional HA-coated surface. Conclusion. In this study we report a new sol-gel technology that can release gentamicin from a bioceramic-coated cementless arthroplasty material. In vitro, local gentamicin levels are in excess of what can be achieved by antibiotic-loaded bone cement. In vivo, bone healing in an animal model is not impaired. This, thus, represents a biomaterial modification that may have the potential to protect at-risk patients from implant-related deep infection. Cite this article: Bone Joint J 2021;103-B(3):522–529


Bone & Joint Open
Vol. 2, Issue 6 | Pages 371 - 379
15 Jun 2021
Davies B Kaila R Andritsos L Gray Stephens C Blunn GW Gerrand C Gikas P Johnston A

Aims. Hydroxyapatite (HA)-coated collars have been shown to reduce aseptic loosening of massive endoprostheses following primary surgery. Limited information exists about their effectiveness in revision surgery. The aim of this study was to radiologically assess osteointegration to HA-coated collars of cemented massive endoprostheses following revision surgery. Methods. Retrospective review of osseointegration frequency, pattern, and timing to a specific HA-coated collar on massive endoprostheses used in revision surgery at our tertiary referral centre between 2010 to 2017 was undertaken. Osseointegration was radiologically classified on cases with a minimum follow-up of six months. Results. In all, 39 patients underwent radiological review at mean 43.5 months; 22/39 (56.4%) showed no osseointegration to the collar. Revision endoprostheses for aseptic loosening were less likely to show osseointegration compared with other indications for revision. Oncological cases with previous or current infection were more likely to show osseointegration to ≥ 1 collar side than those without evidence of prior infection. Conclusion. This seven-year review identified osseointegration of HA-coated collars after revision surgery is less likely (43.6%, 17/39) than after primary surgery. Young patients who undergo revision surgery following initial oncological indication may benefit the most from this collar design. Use in revision oncological cases with a history of infection may be beneficial. HA-coated collars showed limited benefit for patients undergoing revision for failed arthroplasty with history of infection. Cite this article: Bone Jt Open 2021;2(6):371–379


The Bone & Joint Journal
Vol. 103-B, Issue 5 | Pages 958 - 963
3 May 2021
Nguyen NTV Martinez-Catalan N Songy CE Sanchez-Sotelo J

Aims. The purpose of this study was to report bone adaptive changes after anatomical total shoulder arthroplasty (TSA) using a standard-length hydroxyapatite (HA)-coated humeral component, and to report on a computer-based analysis of radiographs to determine changes in peri-implant bone density objectively. Methods. A total of 44 TSAs, performed between 2011 and 2014 using a cementless standard-length humeral component proximally coated with HA, were included. There were 23 males and 21 females with a mean age of 65 years (17 to 65). All shoulders had good quality radiographs at six weeks and five years postoperatively. Three observers graded bone adaptive changes. All radiographs were uploaded into a commercially available photographic software program. The grey value density of humeral radiological areas was corrected to the grey value density of the humeral component and compared over time. Results. Stress shielding was graded as mild in 14 shoulders and moderate in three; the greater tuberosity was the predominant site for stress shielding. The mean metaphyseal and diaphyseal fill-fit ratios were 0.56 (SD 0.1) and 0.5 (SD 0.07), respectively. For shoulders with no radiologically visible stress shielding, the mean decrease in grey value in zones 1 and 7 was 20%, compared with 38% in shoulders with radiologically visible stress shielding. Conclusion. The rate of moderate stress shielding was 7%, five years after implantation of a cementless standard-length HA-coated humeral component. Clinical observation of stress shielding identified on radiographs seems to represent a decrease in grey value of 25% or more. Cite this article: Bone Joint J 2021;103-B(5):958–963


Bone & Joint Research
Vol. 9, Issue 7 | Pages 333 - 340
1 Jul 2020
Mumith A Coathup M Edwards TC Gikas P Aston W Blunn G

Aims. Limb salvage in bone tumour patients replaces the bone with massive segmental prostheses where achieving bone integration at the shoulder of the implant through extracortical bone growth has been shown to prevent loosening. This study investigates the effect of multidrug chemotherapy on extracortical bone growth and early radiological signs of aseptic loosening in patients with massive distal femoral prostheses. Methods. A retrospective radiological analysis was performed on adult patients with distal femoral arthroplasties. In all, 16 patients were included in the chemotherapy group with 18 patients in the non-chemotherapy control group. Annual radiographs were analyzed for three years postoperatively. Dimensions of the bony pedicle, osseointegration of the hydroxyapatite (HA) collar surface, bone resorption at the implant shoulder, and radiolucent line (RLL) formation around the cemented component were analyzed. Results. A greater RLL score (p = 0.041) was observed at three years postoperatively, with those receiving chemotherapy showing greater radiological loosening compared with those not receiving chemotherapy. Chemotherapy patients experience osteolysis at the shoulder of the ingrowth collar over time (p < 0.001) compared with non-chemotherapy patients where osteolysis was not observed. A greater median percentage integration of the collar surface was observed in the non-chemotherapy group (8.6%, interquartile range (IQR) 0.0% to 37.9%; p = 0.021) at three years. Bone growth around the collar was observed in both groups, and no statistical difference in amount of extracortical bony bridging was seen. Conclusion. Multidrug chemotherapy affects the osseointegration of ingrowth collars and accelerates signs of radiological loosening. This may increase the risk of aseptic loosening in patients with massive segmental implants used to treat bone cancer. Cite this article: Bone Joint Res 2020;9(7):333–340


The Bone & Joint Journal
Vol. 101-B, Issue 6_Supple_B | Pages 62 - 67
1 Jun 2019
Tanzer M Chuang PJ Ngo CG Song L TenHuisen KS

Aims. The purpose of this study was to evaluate the biological fixation of a 3D printed porous implant, with and without different hydroxyapatite (HA) coatings, in a canine model. Materials and Methods. A canine transcortical model was used to evaluate the characteristics of bone ingrowth of Ti6Al4V cylindrical implants fabricated using laser rapid manufacturing (LRM). At four and 12 weeks post-implantation, we performed histological analysis and mechanical push-out testing on three groups of implants: a HA-free control (LRM), LRM with precipitated HA (LRM-PA), and LRM with plasma-sprayed HA (LRM-PSHA). Results. Substantial bone ingrowth was observed in all LRM implants, with and without HA, at both time periods. Bone ingrowth increased from 42% to 52% at four weeks, to 60% to 65% at 12 weeks. Mechanical tests indicated a minimum shear fixation strength of 20 MPa to 24 MPa at four weeks, and 34 MPa to 40 MPa at 12 weeks. There was no significant difference in the amount of bone ingrowth or in the shear strength between the three implant types at either time period. Conclusion. At four and 12 weeks, the 3D printed porous implants exhibited consistent bone ingrowth and high mechanical shear strength. Based on the results of this study, we confirmed the suitability of this novel new additive manufacturing porous material for biological fixation by bone ingrowth. Cite this article: Bone Joint J 2019;101-B(6 Supple B):62–67


Bone & Joint Research
Vol. 9, Issue 4 | Pages 182 - 191
1 Apr 2020
D’Ambrosio A Peduzzi L Roche O Bothorel H Saffarini M Bonnomet F

Aims. The diversity of femoral morphology renders femoral component sizing in total hip arthroplasty (THA) challenging. We aimed to determine whether femoral morphology and femoral component filling influence early clinical and radiological outcomes following THA using fully hydroxyapatite (HA)-coated femoral components. Methods. We retrospectively reviewed records of 183 primary uncemented THAs. Femoral morphology, including Dorr classification, canal bone ratio (CBR), canal flare index (CFI), and canal-calcar ratio (CCR), were calculated on preoperative radiographs. The canal fill ratio (CFR) was calculated at different levels relative to the lesser trochanter (LT) using immediate postoperative radiographs: P1, 2 cm above LT; P2, at LT; P3, 2 cm below LT; and D1, 7 cm below LT. At two years, radiological femoral component osseointegration was evaluated using the Engh score, and hip function using the Postel Merle d’Aubigné (PMA) and Oxford Hip Score (OHS). Results. CFR was moderately correlated with CCR at P1 (r = 0.44; p < 0.001), P2 (r = 0.53; p < 0.001), and CFI at P1 (r = − 0.56; p < 0.001). Absence of spot welds (n = 3, 2%) was associated with lower CCR (p = 0.049), greater CFI (p = 0.017), and lower CFR at P3 (p = 0.015). Migration (n = 9, 7%) was associated with lower CFR at P2 (p = 0.028) and P3 (p = 0.007). Varus malalignment (n = 7, 5%), predominantly in Dorr A femurs (p = 0.028), was associated with lower CFR at all levels (p < 0.05). Absence of spot welds was associated with lower PMA gait (p = 0.012) and migration with worse OHS (p = 0.032). Conclusion. This study revealed that femurs with insufficient proximal filling tend to have less favourable radiological outcomes following uncemented THA using a fully HA-coated double-tapered femoral component. Cite this article: Bone Joint Res. 2020;9(4):182–191


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 1 | Pages 34 - 38
1 Jan 2007
Epinette J Manley MT

This study describes 146 primary total knee replacements, either fully or partially coated with hydroxyapatite of which 74 knees in 68 patients were available for clinical and radiological assessment at a mean of 11.2 years (10 to 15). The global failure rate was 1.37% and survival rate with mechanical failure as the end-point was 98.14%. Radiological assessment indicated intimate contact between bone and the hydroxyapatite coating. Over time the hydroxyapatite coating appears to encourage filling of interface gaps remaining after surgery. Our results compare favourably with those of series describing cemented or porous-coated knee replacements, and suggest that fixation with hydroxyapatite is a reliable option in primary total knee replacement


The Bone & Joint Journal
Vol. 101-B, Issue 10 | Pages 1248 - 1255
1 Oct 2019
Pineda A Pabbruwe MB Kop AM Vlaskovsky P Hurworth M

Aims. The aim of this study was to conduct the largest low contact stress (LCS) retrieval study to elucidate the failure mechanisms of the Porocoat and Duofix femoral component. The latter design was voluntarily recalled by the manufacturer. Materials and Methods. Uncemented LCS explants were divided into three groups: Duofix, Porocoat, and mixed. Demographics, polyethylene wear, tissue ingrowth, and metallurgical analyses were performed. Results. In 104 implants, a decrease in the odds of loosening and an increase in metallosis and tissue staining in the Duofix group relative to Porocoat group was detected (p = 0.028). There was an increased presence of embedded metallic debris in the Duofix group (p < 0.001). Decreased tissue ingrowth was associated with the Duofix surface (p < 0.001). The attached beads had reduced microhardness, indicative of adverse thermal processing, which resulted in bead shedding, particulate debris, and metallosis. Conclusion. Hydroxyapatite coating of the LCS femoral component produced unexpected results and led to its recall. The root cause was likely a combination of retained alumina grit and a reduction in bead microhardness (mechanical strength) resulting in increased particle debris, metallosis, and early revision. The Duofix LCS femoral component was not equivalent to the Porocoat version despite its approval through the Food and Drug Administration (FDA) 510(k) equivalance approval process. Regulation of the introduction of modified existing devices needs to be improved and the Duofix LCS should have been considered to be a new device for which equivalence had not been demonstrated at the point of introduction. Cite this article: Bone Joint J 2019;101-B:1248–1255


The Bone & Joint Journal
Vol. 106-B, Issue 3 Supple A | Pages 110 - 114
1 Mar 2024
Yee AHF Chan VWK Fu H Chan P Chiu KY

Aims

The aim of this study was to evaluate the survival of a collarless, straight, hydroxyapatite-coated femoral stem in total hip arthroplasty (THA) at a minimum follow-up of 20 years.

Methods

We reviewed the results of 165 THAs using the Omnifit HA system in 138 patients, performed between August 1993 and December 1999. The mean age of the patients at the time of surgery was 46 years (20 to 77). Avascular necrosis was the most common indication for THA, followed by ankylosing spondylitis and primary osteoarthritis. The mean follow-up was 22 years (20 to 31). At 20 and 25 years, 113 THAs in 91 patients and 63 THAs in 55 patients were available for review, respectively, while others died or were lost to follow-up. Kaplan-Meier analysis was performed to evaluate the survival of the stem. Radiographs were reviewed regularly, and the stability of the stem was evaluated using the Engh classification.


Bone & Joint Research
Vol. 8, Issue 7 | Pages 333 - 341
1 Jul 2019
Grossner TL Haberkorn U Gotterbarm T

Objectives. Bone tissue engineering is one of the fastest growing branches in modern bioscience. New methods are being developed to achieve higher grades of mineral deposition by osteogenically inducted mesenchymal stem cells. In addition to well established monolayer cell culture models, 3D cell cultures for stem cell-based osteogenic differentiation have become increasingly attractive to promote in vivo bone formation. One of the main problems of scaffold-based osteogenic cell cultures is the difficulty in quantifying the amount of newly produced extracellular mineral deposition, as a marker for new bone formation, without destroying the scaffold. In recent studies, we were able to show that . 99m. Tc-methylene diphosphonate (. 99m. Tc-MDP), a gamma radiation-emitting radionuclide, can successfully be applied as a reliable quantitative marker for mineral deposition as this tracer binds with high affinity to newly produced hydroxyapatite (HA). Methods. Within the present study, we evaluated whether this promising new method, using . 99m. Tc-hydroxydiphosphonate (. 99m. Tc-HDP), can be used to quantify the amount of newly formed extracellular HA in a 3D cell culture model. Highly porous collagen type II scaffolds were seeded with 1 × 106 human mesenchymal stem cells (hMSCs; n = 6) and cultured for 21 days in osteogenic media (group A – osteogenic (OSM) group) and in parallel in standard media (group B – negative control (CNTRL) group). After incubation with . 99m. Tc-HDP, the tracer uptake, reflected by the amount of emitted gamma counts, was measured. Results. We saw a higher uptake (up to 15-fold) of the tracer in the OSM group A compared with the CNTRL group B. Statistical analysis of the results (Student`s t-test) revealed a significantly higher amount of emitted gamma counts in the OSM group (p = 0.048). Qualitative and semi-quantitative analysis by Alizarin Red staining confirmed the presence of extracellular HA deposition in the OSM group. Conclusion. Our data indicate that . 99m. Tc-HDP labelling is a promising tool to track and quantify non-destructive local HA deposition in 3D stem cell cultures. Cite this article: T. L. Grossner, U. Haberkorn, T. Gotterbarm. . 99m. Tc-Hydroxydiphosphonate quantification of extracellular matrix mineralization in 3D human mesenchymal stem cell cultures. Bone Joint Res 2019;8:333–341. doi: 10.1302/2046-3758.87.BJR-2017-0248.R1