Martin Williams

A novel ACVR1 mutation in the glycine/serine-rich domain found in the most benign case of a fibrodysplasia ossificans progressiva variant reported to date.

Fibrodysplasia Ossificans Progressiva (FOP) is a rare, autosomal dominant condition, classically characterised by heterotopic ossification beginning in childhood and congenital great toe malformations; occurring in response to a c.617 G > A ACVR1 mutation in the functionally important glycine/serine-rich domain of exon 6. Here we describe a novel c.587 T > C mutation in the glycine/serine-rich domain of ACVR1, associated with delayed onset of heterotopic ossification and an exceptionally mild clinical course. Absence of great toe malformations, the presence of early ossification of the cervical spine facets joints, plus mild bilateral camptodactyly of the 5th fingers, together with a novel ACVR1 mutation, are consistent with the FOP-variant syndrome. The c.587 T > C mutation replaces a conserved leucine with proline at residue 196. Modelling of the mutant protein reveals a steric clash with the kinase domain that will weaken interactions with FKBP12 and induce exposure of the glycine/serine-rich repeat. The mutant receptor is predicted to be hypersensitive to ligand stimulation rather than being constitutively active, consistent with the mild clinical phenotype. This case extends our understanding of the FOP-variant syndrome.

Individuals with high bone mass have an increased prevalence of radiographic knee osteoarthritis

We previously reported an association between high bone mass (HBM) and a bone-forming phenotype of radiographic hip osteoarthritis (OA). As knee and hip OA have distinct risk factors, in this study we aimed to determine (i) whether HBM is also associated with knee OA, and (ii) whether the HBM knee OA phenotype demonstrates a similar pattern of radiographic features to that observed at the hip. HBM cases (defined by DXA BMD Z-scores) from the UK-based HBM study were compared with unaffected family controls and general population controls from the Chingford and Hertfordshire cohort studies. A single blinded observer graded AP weight-bearing knee radiographs for features of OA (Kellgren–Lawrence score, osteophytes, joint space narrowing (JSN), sclerosis) using an atlas. Analyses used logistic regression, adjusting a priori for age and gender, and additionally for BMI as a potential mediator of the HBM–OA association, using Stata v12. 609 HBM knees in 311 cases (mean age 60.8 years, 74% female) and 1937 control knees in 991 controls (63.4 years, 81% female) were analysed. The prevalence of radiographic knee OA, defined as Kellgren–Lawrence grade ≥ 2, was increased in cases (31.5% vs. 20.9%), with age and gender adjusted OR [95% CI] 2.38 [1.81, 3.14], p < 0.001. The association between HBM and osteophytosis was stronger than that for JSN, both before and after adjustment for BMI which attenuated the ORs for knee OA and osteophytes in cases vs. controls by approximately 50%. Our findings support a positive association between HBM and knee OA. This association was strongest for osteophytes, suggesting HBM confers a general predisposition to a subtype of OA characterised by increased bone formation.

Prevalence of radiographic hip osteoarthritis is increased in high bone mass.

Summary Objective Epidemiological studies have shown an association between increased bone mineral density (BMD) and osteoarthritis (OA), but whether this represents cause or effect remains unclear. In this study, we used a novel approach to investigate this question, determining whether individuals with High Bone Mass (HBM) have a higher prevalence of radiographic hip OA compared with controls. Design HBM cases came from the UK-based HBM study: HBM was defined by BMD Z-score. Unaffected relatives of index cases were recruited as family controls. Age-stratified random sampling was used to select further population controls from the Chingford and Hertfordshire cohort studies. Pelvic radiographs were pooled and assessed by a single observer blinded to case-control status. Analyses used logistic regression, adjusted for age, gender and body mass index (BMI). Results 530 HBM hips in 272 cases (mean age 62.9 years, 74% female) and 1702 control hips in 863 controls (mean age 64.8 years, 84% female) were analysed. The prevalence of radiographic OA, defined as Croft score ≥3, was higher in cases compared with controls (20.0% vs 13.6%), with adjusted odds ratio (OR) [95% CI] 1.52 [1.09, 2.11], P = 0.013. Osteophytes (OR 2.12 [1.61, 2.79], P < 0.001) and subchondral sclerosis (OR 2.78 [1.49, 5.18], P = 0.001) were more prevalent in cases. However, no difference in the prevalence of joint space narrowing (JSN) was seen (OR 0.97 [0.72, 1.33], P = 0.869). Conclusions An increased prevalence of radiographic hip OA and osteophytosis was observed in HBM cases compared with controls, in keeping with a positive association between HBM and OA and suggesting that OA in HBM has a hypertrophic phenotype.

Osteophytes, Enthesophytes, and High Bone Mass: A Bone-Forming Triad With Potential Relevance in Osteoarthritis

Previous studies of skeletal remains have suggested that both enthesophytes and osteophytes are manifestations of an underlying bone‐forming tendency. A greater prevalence of osteophytes has been observed among individuals with high bone mass (HBM) compared with controls. This study was undertaken to examine the possible interrelationships between bone mass, enthesophytes, and osteophytes in a population of individuals with extreme HBM.

Incarceration of the medial collateral ligament in the intercondylar notch following proximal avulsion

Intra-articular entrapment of the medial collateral ligament (MCL) is a rare but recognised complication of traumatic injury to the posteromedial corner (PMC) of the knee. Considering the MCL is the most commonly injured ligament of the knee this complication is extremely rare with only a handful of cases describing MCL entrapment following distal avulsion of the MCL. We present the first known case of MCL entrapment following proximal avulsion of the MCL and posterior oblique ligament (POL) with the mid-substance of the MCL becoming entrapped in the joint, lying on the superior surface of the medial meniscus and extending up into the intercondylar notch. In addition, the medial patellar retinaculum was also entrapped in the medial aspect of the medial patellofemoral joint. MCL entrapment is best treated with expeditious surgical intervention and it is therefore crucial that the MRI findings are not overlooked. Details of the clinical assessment, MRI and operative findings are presented with a literature review of MCL entrapment.

High Bone Mass is associated with bone-forming features of osteoarthritis in non-weight bearing joints independent of body mass index

Objectives High Bone Mass (HBM) is associated with (a) radiographic knee osteoarthritis (OA), partly mediated by increased BMI, and (b) pelvic enthesophytes and hip osteophytes, suggestive of a bone-forming phenotype. We aimed to establish whether HBM is associated with radiographic features of OA in non-weight-bearing (hand) joints, and whether such OA demonstrates a bone-forming phenotype. Methods HBM cases (BMD Z-scores ≥ + 3.2) were compared with family controls. A blinded assessor graded all PA hand radiographs for: osteophytes (0–3), joint space narrowing (JSN) (0–3), subchondral sclerosis (0–1), at the index Distal Interphalangeal Joint (DIPJ) and 1st Carpometacarpal Joint (CMCJ), using an established atlas. Analyses used a random effects logistic regression model, adjusting a priori for age and gender. Mediating roles of BMI and bone turnover markers (BTMs) were explored by further adjustment. Results 314 HBM cases (mean age 61.1 years, 74% female) and 183 controls (54.3 years, 46% female) were included. Osteophytes (grade ≥ 1) were more common in HBM (DIPJ: 67% vs. 45%, CMCJ: 69% vs. 50%), with adjusted OR [95% CI] 1.82 [1.11, 2.97], p = 0.017 and 1.89 [1.19, 3.01], p = 0.007 respectively; no differences were seen in JSN. Further adjustment for BMI failed to attenuate ORs for osteophytes in HBM cases vs. controls; DIPJ 1.72 [1.05, 2.83], p = 0.032, CMCJ 1.76 [1.00, 3.06], p = 0.049. Adjustment for BTMs (concentrations lower amongst HBM cases) did not attenuate ORs. Conclusions HBM is positively associated with OA in non-weight-bearing joints, independent of BMI. HBM-associated OA is characterised by osteophytes, consistent with a bone-forming phenotype, rather than JSN reflecting cartilage loss. Systemic factors (e.g. genetic architecture) which govern HBM may also increase bone-forming OA risk.

Acute calcific periarthiritis of the knee presenting with calcification within the lateral collateral ligament

A 71-year-old woman was admitted with acute swelling of the right knee, pain on the lateral aspect and restricted movement. There was no instability or locking. She had no history of trauma and was generally in good health. Plain radiographs demonstrated a calcific opacity adjacent to the lateral femoral condyle. This was shown to be within the lateral collateral ligament (LCL) at ultrasound and MRI. A diagnosis of acute calcific periarthritis (ACP) was made. The patients symptoms resolved within a few weeks with simple analgaesia. ACP presenting with calcification within the LCL is rare. It is important to recognise the clinical and imaging findings of this condition as it may mimic other more serious pathologies such as infection and gout. This may result in unnecessary investigations, misdiagnoses and incorrect treatments.

Osteochondroma of the clavicle causing Horner's syndrome.

A 17-year-old girl was admitted with a 1-year history of right-sided headaches and unilateral ptosis for 6u2005months. She was diagnosed with Horners syndrome. Ultrasound and CT scan demonstrated an osteochondroma of the posterosuperior aspect of the medial clavicle compressing adjacent structures, including the right internal jugular vein and right common carotid artery. Cartilage sequence MRI showed an osteochondroma with a 5u2005mm cartilage cap. There were no suspicious features of malignancy. The patient was referred to a specialist centre for surgical resection. Osteochondroma of the clavicle presenting with Horners syndrome is extremely rare, with only one previously reported case. In this case report, we discuss the anatomy of the oculosympathetic chain, which consists of a three neuron arc. The disruption of the neuronal arc, at any point, may result in Horners syndrome. We also discuss the various causes of Horners syndrome and its radiological investigation.

Osteophytes, enthesophytes and High Bone Mass; A bone-forming triad with relevance for osteoarthritis >

Previous studies of skeletal remains have suggested that both enthesophytes and osteophytes are manifestations of an underlying bone‐forming tendency. A greater prevalence of osteophytes has been observed among individuals with high bone mass (HBM) compared with controls. This study was undertaken to examine the possible interrelationships between bone mass, enthesophytes, and osteophytes in a population of individuals with extreme HBM.

Osteophytes, Enthesophytes, and High Bone Mass: A Bone-Forming Triad With Potential Relevance in Osteoarthritis: Osteophytes, Enthesophytes, and High Bone Mass in OA

Previous studies of skeletal remains have suggested that both enthesophytes and osteophytes are manifestations of an underlying bone‐forming tendency. A greater prevalence of osteophytes has been observed among individuals with high bone mass (HBM) compared with controls. This study was undertaken to examine the possible interrelationships between bone mass, enthesophytes, and osteophytes in a population of individuals with extreme HBM.