Response of the ENPP1-Deficient Skeletal Phenotype to Oral Phosphate Supplementation and/or Enzyme Replacement Therapy: Comparative Studies in Humans and Mice

Inactivating mutations in human ecto-nucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1) may result in early-onset osteoporosis (EOOP) in haploinsufficiency and autosomal recessive hypophosphatemic rickets (ARHR2) in homozygous deficiency. ARHR2 patients are frequently treated with phosphate supplementation to ameliorate the rachitic phenotype, but elevating plasma phosphorus concentrations in ARHR2 patients may increase the risk of ectopic calcification without increasing bone mass. To assess the risks and efficacy of conventional ARHR2 therapy, we performed comprehensive evaluations of ARHR2 patients at two academic medical centers and compared their skeletal and renal phenotypes with ENPP1-deficient Enpp1^asj/asj mice on an acceleration diet containing high phosphate treated with recombinant murine Enpp1-Fc. ARHR2 patients treated with conventional therapy demonstrated improvements in rickets, but all adults and one adolescent analyzed continued to exhibit low bone mineral density (BMD). In addition, conventional therapy was associated with the development of medullary nephrocalcinosis in half of the treated patients. Similar to Enpp1^asj/asj mice on normal chow and to patients with mono- and biallelic ENPP1 mutations, 5-week-old Enpp1^asj/asj mice on the high-phosphate diet exhibited lower trabecular bone mass, reduced cortical bone mass, and greater bone fragility. Treating the Enpp1^asj/asj mice with recombinant Enpp1-Fc protein between weeks 2 and 5 normalized trabecular bone mass, normalized or improved bone biomechanical properties, and prevented the development of nephrocalcinosis and renal failure. The data suggest that conventional ARHR2 therapy does not address low BMD inherent in ENPP1 deficiency, and that ENPP1 enzyme replacement may be effective for correcting low bone mass in ARHR2 patients without increasing the risk of nephrocalcinosis. © 2021 American Society for Bone and Mineral Research (ASBMR).     

Anterior cruciate ligament injury about 20 years post‐treatment: A kinematic analysis of one‐leg hop

Reduced dynamic knee stability, often evaluated with one‐leg hops (OLHs), is reported after anterior cruciate ligament (ACL) injury. This may lead to long‐standing altered movement patterns, which are less investigated. 3D kinematics during OLH were explored in 70 persons 23 ± 2 years after ACL injury; 33 were treated with physiotherapy in combination with ACL reconstruction (ACL_R) and 37 with physiotherapy alone (ACL_PT). Comparisons were made to 33 matched controls. We analyzed (a) maximal knee joint angles and range of motion (flexion, abduction, rotation); (b) medio‐lateral position of the center of mass (COM) in relation to knee and ankle joint centers, during take‐off and landing phases. Unlike controls, ACL‐injured displayed leg asymmetries: less knee flexion and less internal rotation at take‐off and landing and more lateral COM related to knee and ankle joint of the injured leg at landing. Compared to controls, ACL_R had larger external rotation of the injured leg at landing. ACL_PT showed less knee flexion and larger external rotation at take‐off and landing, and larger knee abduction at Landing. COM was more medial in relation to the knee at take‐off and less laterally placed relative to the ankle at landing. ACL injury results in long‐term kinematic alterations during OLH, which are less evident for ACL_R.     

Spontaneous splenic vein aneurysm rupture in the puerperium

A case of intra- and retroperitoneal haemorrhage after a splenic vein aneurysm rupture is described. A 27-year-old woman complained of chest pain on her first postpartum day. Symptoms were initially suggestive of pulmonary embolism, but within 3 h she developed severe acute abdominal pain, abdominal distension and haemodynamic instability. Ultrasound demonstrated a non-echogenic mass in the abdomen suggestive of a fluid collection and a computed tomography scan confirmed the presence of a lesion at the pancreatic tail. Urgent laparotomy revealed splenic vein rupture near the pancreatic tail. Partial pancreatectomy and splenectomy were performed. The patient subsequently made an uneventful recovery. Histological examination revealed a splenic vein aneurysm and chronic inflammatory changes in the pancreatic tissue. Rupture of a splenic vein aneurysm is a rare event and the diagnosis may present difficulty because its presentation is similar to several other more common conditions. However, rupture of a splenic vein aneurysm should be suspected in any pregnant woman with unexplained abdominal pain or with clear signs of haemorrhage, as delay in diagnosis can have devastating consequences.     

Internal fixation and muscle pedicle bone grafting in femoral neck fractures

Background:

The treatment of displaced intracapsular femoral neck fracture is still an unsolved problem. Non-union and avascular necrosis are the two main complications of this fracture, especially if patient presents late. Muscle pedicle bone grafting has been advocated to provide additional blood supply. We present analysis of our 32 cases of displaced femoral neck fracture treated by internal fixation and quadratus femoris based muscle pedicle bone grafting.

Materials and Methods:

Open reduction and internal fixation with muscle pedicle grafting was done in 32 patients. The age of patients varied from 14-62 years (average age 45 years) with male to female ratio of 13:3. Twenty-nine fractures were more than three weeks old. All the cases were treated by Meyers'' procedure. The fracture was internally fixed after open reduction and then a muscle pedicle graft was applied. It was supplemented by cancellous bone graft in seven cases. Fixation was done by parallel cancellous lag screws (n = 19), crossed Garden''s screws (n = 7), parallel Asnis screws (n = 5) and Moore''s pin (n = 1).Quadratus femoris muscle pedicle graft was used in 32 cases. In the initial 12 cases the graft was fixed with circumferential proline sutures, but later, to provide a secure fixation, the graft was fixed with a cancellous screw (n = 20). Postoperative full weight bearing was deferred to an average of 10 weeks.

Results:

Union was achieved in 26/29 (89.65%) cases which could be followed for an average period of 3.4 years, (2-8.5 years) with good functional results and had the ability to squat and sit cross-legged. Results were based on hip rating system given by Salvatti and Wilson. The results were excellent in 15 cases, good in four cases, fair in four cases and poor in six cases. Complications were avascular necrosis (n = 2), transient foot drop (n = 2), coxa-vara (n = 1) and temporary loss of scrotal sensation (n = 1).

Conclusion:

Muscle pedicle bone grafting with internal fixation is a viable treatment option in displaced femoral neck fractures with late presentation.