Black Bone Disease of the Foot: A Two-Year Follow-Up Case Study

“Black bone disease” is a term commonly used to describe a condition characterized by a blue/green/brown discoloration to the bone that often resembles infracted or necrotic bone. The chronic use of minocycline or tetracycline has been reported in previous data as a cause of this discoloration to the skin, bone, and teeth. However, the occurrence in bone is rare, with few studies reported regarding the discoloration. We previously presented a case of this condition encountered during cheilectomy of the first metatarsophalangeal joint in a patient who had had long-term usage of minocycline for adult acne. Two years after the initial case, the patient returned for correction of a hammertoe deformity on the second left proximal phalanx of the same foot. We present the findings and photographs from the second surgery. In addition, we have provided the relevant case data and figures from the first case for ease of comparison.     

Green Bone: Minocycline-Induced Discoloration of Bone Rarely Reported in Foot and Ankle

The tetracycline antibiotics incorporate into bone similar to bisphosphonates. Tetracycline stains bone a fluorescent yellow and minocycline, more commonly used for chronic acne, stains bone dark green. Owing to its frequent use, the occurrence of green bone discoloration due to antibiotics in the tetracycline class is well understood. Its pigmentation can be seen through delicate, thin tissue as a dark blue-gray. Histologic inspection of this bone will confirm a benign condition without evidence of bone disease. Although yellow and green discoloration has been documented frequently in association with oral surgery, it has been reported less commonly in the lower extremity. Green discoloration of bone has rarely been reported in the foot and ankle. Unlike other forms of hyperpigmentation of the skin and bone, this entity is benign when resulting from tetracycline therapy. It is always prudent to have a clinical correlate for an unusual discoloration or hyperpigmentation of any tissue when it exists. In the absence of a definitive clinical correlation, a biopsy is warranted. The following case studies provide a pictoral of green bone as it was encountered in the foot and ankle of 2 young adult females undergoing surgery.     

Minocycline-induced black bone disease with synovial pigmentation in a patient undergoing revision anterior cruciate ligament surgery: A case report

IntroductionLong-term use of minocycline at high doses is associated with hyperpigmentation with multiple sites of involvement. While the cutaneous organs and the oral cavity are most commonly affected, bone discoloration is a rare entity.Case presentationA 19-year-old male patient with a history of acne vulgaris and intermittent treatment with high dose minocycline for three years presented with recurrent anterior cruciate ligament (ACL) tear. During arthroscopic surgery, however, hyperpigmentation of the femur and synovium was observed. Abnormal tissue was biopsied and confirmed through histopathological examination to contain melanin-related minocycline pigmentation. Revision surgery was re-scheduled with no intraoperative complications and excellent long-term clinical outcomes.Clinical discussionThere are several possible causes of hyperpigmentation, including hemosiderin deposition, infection, aseptic necrosis, demineralization, and metastatic disease. Black bone disease, caused by minocycline-induced hyperpigmentation, is rare. While the appearance is grossly abnormal in black bone disease, there has been no evidence suggesting that tissue integrity is compromised.ConclusionThis case confirms that hyperpigmentation does not affect bone integrity and that surgical procedures can be performed safely. Knowing the adverse effects of minocycline administration could reduce inappropriate postponement of surgical procedures, thereby saving time and resources.     

Bone Preservation in Total Hip Arthroplasty

BackgroundPreserving bone stock in younger and more active patients after total hip arthroplasty (THA) is important for future revision. Newer prosthesis designs, including short femoral stems and isoelastic acetabular cups, are likely to preserve more bone stock. However, long-term follow-up studies on bone remodeling after short-stem THA with an isoelastic monoblock acetabular cup are few. Therefore, we evaluated bone preservation after THA using these prostheses at a 5-year follow-up.MethodsThis prospective observational study is a 5-year follow-up of our previously reported 2-year observational study on the same cohort of patients. We included 45 patients with primary osteoarthritis treated with a calcar-guided femoral short-stem prosthesis and a monoblock press-fit acetabular cup. We evaluated bone mineral density (BMD) around the prostheses using dual-energy X-ray absorptiometry and reported functional outcomes preoperatively and at 3, 12, 24, and 60 months postoperatively. All complications were recorded.ResultsAt the final follow-up, the BMD was comparable with that at 24 months in Gruen zones 3, 4, 5, 6, and 7, whereas it significantly differed in Gruen zones 1 (P < .0001) and 2 (P < .004). On the acetabular side, the BMD leveled off similarly in all DeLee and Charnley zones between 24 and 60 months (P > .05). Moreover, all measured clinical outcomes significantly improved (P < .001). One perioperative dislocation was reported.ConclusionPatients undergoing THA with a calcar-guided femoral short-stem prosthesis and a monoblock acetabular cup can expect preservation of bone stock over a longer follow-up with excellent clinical outcomes and few complications.     

Genetic Background Modifies the Effects of Type 2 Cannabinoid Receptor Deficiency on Bone Mass and Bone Turnover

Cannabinoid receptors and their ligands play significant roles in regulating bone metabolism. Previous studies of type 1 cannabinoid receptor-deficient mice have shown that genetic background influences the skeletal phenotype. Here, we investigated the effects of genetic background on the skeletal phenotype of mice with type 2 cannabinoid receptor deficiency (Cnr2 ^?/?). We studied Cnr2 ^?/? mice on a CD1 background and compared the findings with those previously reported in Cnr2 ^?/? C57BL/6 mice. Young female Cnr2 ^?/? CD1 mice had low bone turnover and high trabecular bone mass compared with wild-type (WT), contrasting with the situation in Cnr2 ^?/? C57BL/6 mice where trabecular bone mass has been reported to be similar to WT. The Cnr2 ^?/? CD1 mice lost more trabecular bone at the tibia with age than WT due to reduced bone formation, and at 12 months there was no difference in trabecular bone volume between genotypes. This differs from the phenotype previously reported in C57BL/6 Cnr2 ^?/? mice, where bone turnover is increased and bone mass reduced with age. There were no substantial differences in skeletal phenotype between Cnr2 ^?/? and WT in male mice. Cortical bone phenotype was similar in Cnr2 ^?/? and WT mice of both genders. Deficiency of Cnr2 has site- and gender-specific effects on the skeleton, mainly affecting trabecular bone, which are influenced by genetic differences between mouse strains. Further evaluation of the pathways responsible might yield new insights into the mechanisms by which cannabinoid receptors regulate bone metabolism.     

Case Study: An intraoperative finding of black bone disease in a podiatric surgery patient

Black bone disease has been recognised as a potential consequence of long-term treatment with tetracycline antibiotics. Largely documented affecting structures in the head and skull, there are few reported cases of black bone disease in the foot and ankle. The case of a 55 years old patient, who as a teenager, had undergone treatment with minocycline hydrochloride for chronic acne, and was found to have bone discolouration consistent with minocycline induced black bone disease (MIBBD) during the course of hallux valgus corrective surgery some 40 years later, is presented. In spite of the intraoperative findings, the patient’s post-operative recovery and bone healing was uneventful. The literature on minocycline induced black bone disease is reviewed.     

Thirty-Year Follow-Up of Patient With Gorham Disease (Massive Osteolysis) Treated With Hip Arthroplasty

Gorham disease (also known as massive osteolysis or disappearing bone disease) is an exceedingly rare, peculiar entity of uncertain cause and unpredictable prognosis. There is no proven mode of therapy or consensus on treatment. We present 30-year follow-up on a patient successfully treated with resection, total hip arthroplasty, and radiation with no recurrence of disease. Our observations in this case suggest that surgical treatment and reconstruction can lead to good long-term function and disease-free survival.     

Staining of endotracheal tube with isosulfan blue dye after sentinel node mapping: a case report

Sentinel node mapping is successfully performed for the detection of cancer and nodal metastasis. There is a reported complication rate of 1.5%, most being mild allergic reactions, with a few rare reported cases of anaphylaxis. Isosulfan blue has been found to routinely create a modest artifactual desaturation via pulse oximetry, as well as a transient skin discoloration that may last for several hours to weeks. It causes discoloration of urine and has been detected in other body secretions, none of which have been found to be of clinical significance. This is a case report involving a 61-year-old woman who underwent sentinel node mapping and axillary dissection for breast adenocarcinoma. On postoperative extubation, the endotracheal tube was noted to be stained dark blue with isosulfan dye. This unusual complication is unreported to date and is likely the result of systemic absorption of the dye.     

Ankle-Brachial Index and Bone Turnover in Patients on Dialysis

An association between atherosclerosis and osteoporosis has been reported in several studies. This association could result from local intraosseous atherosclerosis and ischemia, which is shown by limb osteoporosis in patients with peripheral artery disease (PAD), but also could result from bidirectional communication between the skeleton and blood vessels. Systemic bone disorders and PAD are frequent in ESRD. Here, we investigated the possible interaction of these disorders. For 65 prevalent nondiabetic patients on hemodialysis, we measured ankle-brachial pressure index (ABix) and evaluated mineral and bone disorders with bone histomorphometry. In prevalent patients on hemodialysis, PAD (ABix<0.9 or >1.4/incompressible) was associated with low bone turnover and pronounced osteoblast resistance to parathyroid hormone (PTH), which is indicated by decreased double-labeled surface and osteoblast surface (P<0.001). Higher osteoblast resistance to PTH in patients with PAD was characterized by weaker correlation coefficients (slopes) between serum PTH and double-labeled surface (P=0.02) or osteoblast surface (P=0.03). The correlations between osteoclast number or eroded surface and serum mineral parameters, including PTH, did not differ for subjects with normal ABix and PAD. Common vascular risk factors (dyslipidemia, smoking, and sex) were similar for normal, low, and incompressible ABix. Patients with PAD were older and had high C-reactive protein levels and longer hemodialysis vintage. These results indicate that, in prevalent nondiabetic patients with ESRD, PAD associates with low bone turnover and pronounced osteoblast resistance to PTH.     

Green urine: A bezoar effect

The green color in urine may suggest the presence of a severe pathology needing treatment. Many different potential causes of green urine have previously been reported. In our case, after ruling out other potential causes of green urine, it was suggested that the surgical manipulation of the paralytic ileum might have induced the reabsorption of the methylene blue which had been retained in the bowel (bezoar effect), even 96 hours after the nasogastric administration.ConclusionsThe staff should keep in mind this possible effect due to methylene blue to recognize early and avoid unnecessary laboratory tests.Authors summaryThis case report illustrates the significance of urine discoloration, sometimes indicate the presence of a systemic disorder and some rare cases, this phenomenon has no pathologic effects. To our knowledge, this is the first case report of a green urine by drug bezoar due methylene blue in children.     

An unusual presentation of whiplash injury: long thoracic and spinal accessory nerve injury

Whiplash injuries from motor vehicle accidents are very common. The usual presentation and course of this condition normally results in resolution of symptoms within a few weeks. Brachial plexus traction injuries without any bone or joint lesion of the cervical spine have been reported before. We report a case where a gentleman was involved in a rear end vehicle collision, sustained a whiplash injury and was later found to have a long thoracic nerve palsy and spinal accessory nerve palsy. Although isolated injuries of both nerves following a whiplash injury have been reported, combined injury of the two nerves following a whiplash injury is very uncommon and is being reported for the first time.

     

Bone repair in osteoporotic bone: postmenopausal and cortisone-induced osteoporosis

Although osteoporosis has been the subject of a considerable number of publications in recent years, very few studies have investigated the effects of osteopososis on the process of tissue repair. Most of the studies are based on animal data, using the ovariectomized rat model, and in most cases, fractures were obtained by femoral osteotomy. This model is imperfect in several aspects to fit with postmenopausal osteoporosis which is a complex, multifactorial disorder. Furthermore, a surgically induced fracture is not exactly the same as a fracture which occurs as a result of bone fragility. However, and despite contradictory results in some of the studies, in ovariectomized rats a delay in bone consolidation has been reported in the model, associated locally with a decrease in bone mineral density and mechanical resistance. Very few human data are available, which confirm the existence of a delay in consolidation subsequent to femoral fractures in aged patients compared to young patients.     

Fistula of submaxillary gland following excision of thyroglossal cyst

A case of external submaxillary gland fistula opening through the midline of the neck anteriorly, midway between the thyroid cartilage and hyoid bone and following operations for excision of thyroglossal cyst and excision of thyroglossal sinus, is reported. Cure was obtained by removing the fistulous tract along with the left submaxillary gland through an incision as recommended by Sistrunk for the excision of a thyroglossal sinus. The occurrence of the submaxillary gland fistula is believed to have been due to branching of the thyroglossal tract at or near the hyoid bone and to operative trauma to the left submaxillary gland as a result of discoloration of normal tissue adjacent to the thyroglossal tract by the use of methylene blue for injection into the cyst prior to the initial operation.     

The Impact of Smoking on Bone Metabolism,Bone Mineral Density and Vertebral Fractures in Postmenopausal Women

Background: Smoking is recognized among the risk factors for osteoporosis, but only few studies have comprehensively explored its influence on bone metabolism and strength. We aimed to evaluate smoking effects on calcium-phosphate metabolism, bone mineral density (BMD) and fracture risk in postmenopausal women. Methods: Our sample included 1067 postmenopausal women who arrived to our osteoporosis outpatient clinic. Anamnestic data, smoking habits (categorized as never, former, and current; and by smoking intensity and duration), biochemical parameters, lumbar/femoral BMD, and presence of vertebral fractures were recorded. In a subsample of 357 women, the changes in BMD after a 2-yr follow-up period were also assessed. Results: Current smokers had shorter reproductive age, lower body mass index, and higher prevalence of heavy alcohol consumption than former/never smokers. They also had lower PTH values and weaker linear association between serum vitamin D and parathyroid hormone (current β = −0.11[SE = 0.004]; former β = −0.14[SE = 0.01]; never β = −0.20[SE = 0.003]; p < 0.01 for all). Baseline BMD did not reflect differences based on smoking habits, duration or intensity. However, after 2 years, only current smokers significantly worsened in femural BMD. After adjustment for confounders, the chance of having sustained vertebral fractures at the first evaluation increased by 74% (95% confidence interval:1.07–2.83) in current compared with never smokers, especially among heavy smokers. Conclusions: Smoking may negatively affect bone by inhibiting vitamin D-parathyroid hormone axis, reducing estrogen exposure, promoting risky health behaviors, and accelerating bone loss, especially at the femur. No significant differences were observed in these outcomes among former smokers, suggesting that quitting smoking has beneficial effects on bone health.     

Hepcidin1 Knockout Mice Display Defects in Bone Microarchitecture and Changes of Bone Formation Markers

Iron accumulation is a risk factor of osteoporosis; mechanisms leading to iron-related bone loss are not fully determined. We sought to better understand the effect of chronic iron accumulation on bone over the life span in a mouse model. Hepcidin1 knockout (Hepc1 ^?/?) male mice and their littermate control wild type (WT) mice at 7 months old were used in this study. Serum iron and ferritin as well as iron contents in liver and femur were significantly increased in Hepc1 ^?/? mice compared to WT mice. We found that Hepc1 ^?/? mice had a phenotype of low bone mass and alteration of the bone microarchitecture, most likely caused by a decreased osteoblastic activity. Cell culture studies indicated that chronic iron accumulation decreased bone formation, probably by affecting bone morphogenetic protein signaling.     

Minocycline-induced Periarticular Black Bones in Inflamed Joints Which Underwent Arthroplastic Reconstruction

Background

Minocycline-induced pigmentation of bone (black bone) is well described in tooth-bearing intra-oral bone, but is less known in periarticular bone in patients who have undergone total joint arthroplasty. On a retrospective basis, we investigated the short-term clinico-radiological results of total joint arthroplasties in which the patient developed minocycline-induced periarticular black bone.

Methods

We found 5 cases (0.08%), in 4 patients, of periarticular bone pigmentation revealed during total joint arthroplasties (2 hips, 2 knees, and 1 ankle) in our series of total joint surgeries (6,548 cases) over a 10-year time period in our 3 institutes. Their mean age was 56 years at surgery. All patients had received long-term minocycline treatment. Mean dosage and duration of minocycline was 160 mg/day and 2.2 years, respectively. Minocycline had been prescribed for reactive arthritis (one), rheumatoid arthritis (two) and late infection after total joint arthroplasty (two patients). Mean follow-up period was 3.4 years after the surgeries.

Results

All cases had black or brown pigmentation in the periarticular bones during the surgery. There was no pigmentation in the cartilage or soft tissues of the joints. The mean Japanese Orthopaedic Association (JOA) score or Japanese Society for Surgery of the Foot (JSSF) scale for rheumatoid arthritis foot and ankle joints at latest follow-up (case 1, 66; case 2, 87; case 3, 77; case 4, 77; case 5, 80) improved compared to those of pre-surgery (case 1, 47; case 2, 45; case 3, 55; case 4, 34; case 5, 55). No implant loosening was noted on radiographic examination during the follow-up period. No abnormal bone formation, bone necrosis, hemosiderin deposition, malignancy or metallic debris was found on histological examination.

Conclusions

No clinico-radiological symptoms of total joint arthroplasties showed in the patients with minocycline-induced periariticular black bone in the short-term. Systemic minocycline treatment has the potential to induce significant black pigmentation of many tissues. In particular, minocycline-induced pigmentation of periarticular bone may be accelerated by inflammation due to rheumatic or pyogenic arthritis. Surgeons should recognize the risk of bone pigmentation in inflamed joints due to the systemic treatment of minocycline and explore its influence on periarticular bone and total joint arthroplasty in the long-term.     

Bone wax can cause foreign body granuloma in the medulla oblongata

Bone wax is commonly used in neurosurgical practice as a haemostatic and sealing agent. It is a safe agent, but may lead to adverse effects such as infection, epistaxsis, allergic reaction or foreign body granuloma. There are very few reported cases of the neurological complications of remnant bone wax in the subdural or subarachnoid space. The authors report the case of a foreign body granuloma infiltration through the medulla oblongata due to remnant bone wax in the subarachnoid space after posterior fossa decompressive surgery.     

Comparison of the Relationship Between Bone Marrow Adipose Tissue and Volumetric Bone Mineral Density in Children and Adults

Several large-scale studies have reported the presence of an inverse relationship between bone mineral density (BMD) and bone marrow adipose tissue (BMAT) in adults. We aim to determine if there is an inverse relationship between pelvic volumetric BMD (vBMD) and pelvic BMAT in children and to compare this relationship in children and adults. Pelvic BMAT and bone volume (BV) was evaluated in 181 healthy children (5–17 yr) and 495 healthy adults (≥18 yr) with whole-body magnetic resonance imaging (MRI). Pelvic vBMD was calculated using whole-body dual-energy X-ray absorptiometry to measure pelvic bone mineral content and MRI-measured BV. An inverse correlation was found between pelvic BMAT and pelvic vBMD in both children (r = −0.374, p < 0.001) and adults (r = −0.650, p < 0.001). In regression analysis with pelvic vBMD as the dependent variable and BMAT as the independent variable, being a child or adult neither significantly contribute to the pelvic BMD (p = 0.995) nor did its interaction with pelvic BMAT (p = 0.415). The inverse relationship observed between pelvic vBMD and pelvic BMAT in children extends previous findings that found the inverse relationship to exist in adults and provides further support for a reciprocal relationship between adipocytes and osteoblasts.     

Influence of Physical Activity on Bone Strength in Children and Adolescents: A Systematic Review and Narrative Synthesis

A preponderance of evidence from systematic reviews supports the effectiveness of weight‐bearing exercises on bone mass accrual, especially during the growing years. However, only one systematic review (limited to randomized controlled trials) examined the role of physical activity (PA) on bone strength. Thus, our systematic review extended the scope of the previous review by including all PA intervention and observational studies, including organized sports participation studies, with child or adolescent bone strength as the main outcome. We also sought to discern the skeletal elements (eg, mass, structure, density) that accompanied significant bone strength changes. Our electronic‐database, forward, and reference searches yielded 14 intervention and 23 observational studies that met our inclusion criteria. We used the Effective Public Health Practice Project (EPHPP) tool to assess the quality of studies. Due to heterogeneity across studies, we adopted a narrative synthesis for our analysis and found that bone strength adaptations to PA were related to maturity level, sex, and study quality. Three (of five) weight‐bearing PA intervention studies with a strong rating reported significantly greater gains in bone strength for the intervention group (3% to 4%) compared with only three significant (of nine) moderate intervention studies. Changes in bone structure (eg, bone cross‐sectional area, cortical thickness, alone or in combination) rather than bone mass most often accompanied significant bone strength outcomes. Prepuberty and peripuberty may be the most opportune time for boys and girls to enhance bone strength through PA, although this finding is tempered by the few available studies in more mature groups. Despite the central role that muscle plays in bones' response to loading, few studies discerned the specific contribution of muscle function (or surrogates) to bone strength. Although not the focus of the current review, this seems an important consideration for future studies. © 2014 American Society for Bone and Mineral Research.     

Porphyrin-adsorbed Allograft Bone: A Photoactive,Antibiofilm Surface

Background

Allograft bone is commonly used to augment bone stock. Unfortunately, allograft is prone to bacterial contamination and current antimicrobial therapies are inadequate. Photoactivated porphyrins combat bacterial growth by production of reactive oxygen species (ROS); however, to our knowledge, they have not been tested in the setting of allograft bone.

Questions/purposes

We asked: (1) Does 5,10,15,20-tetrakis-(4-aminophenyl)-porphyrin (TAPP) stably adsorb to morselized, mineralized allograft? (2) Does Staphylococcus aureus acquire TAPP from TAPP-allograft? (3) Is TAPP-allograft antibacterial to S. aureus? (4) Is ROS production critical for antimicrobial activity? (5) Does illuminated TAPP-allograft dislodge biofilm? (6) Could other photoactive dyes (TAPP, TMPyP, TSP, THP, and methylene blue) confer antimicrobial properties to allograft?

Methods

TAPP adsorption to allograft (TAPP-allograft), its localization in S. aureus, and TAPP-allograft long-term stability were determined spectrophotometrically. Antimicrobial activity was measured while activated with light or in the dark during incubation with S. aureus or after allograft biofilm formation. Glutathione was added to illuminated TAPP-allograft to quench ROS and antimicrobial activity was determined. Light-dependent antimicrobial activity of other photoactive dyes (TMPyP, TSP, THP, and methylene blue) adsorbed to allograft was also tested.

Results

We found (1) porphyrins strongly adhere to bone allograft; and (2) the bacteria are not able to sequester TAPP from the TAPP-allograft; (3) when illuminated, TAPP-allograft is resistant to bacterial adherence; (4) the effects of TAPP are inhibited by the radical scavenger glutathione, indicating ROS-dependent antimicrobial activity; (5) illumination of TAPP-allograft disrupts biofilms; and, (6) other photoactive dyes impede biofilm formation on allograft bone in the presence of light.

Conclusions

Porphyrins stably associate with allograft and are inactive until illuminated. Illuminated TAPP-allograft markedly reduces bacterial colonization, which is restored in the presence of radical scavengers. Finally, illuminated TAPP-allograft disrupts biofilms.

Clinical Relevance

The findings of this in vitro study suggest that loading bone allograft with biocompatible porphyrins before surgery might allow increased sterility of the allograft during implantation. Future testing in an animal model will determine if these in vitro activities can be used to prevent allograft-based infection in an establishing osteomyelitis.