Conasequences on bone and metabolism of severe hyperparathyroidism in chronic kidney disease

1. 1
Dr Yogendranath Purrunsing
Uremic Leontiasis Ossea

2. Uremic Leontiasis Ossea
Leontiasis ossea, also known as leontiasis or lion
face, is a form of severe bone remodeling that
prevails in patients with chronic kidney disease
(CKD) and secondary hyperparathyroidism
(SHPT), renal osteodystrophy, Paget diseases,
and fibrous dysplasia, characterized by
craniofacial, ribs, long bones, and spine
deformations.

3. The famed Rudolf Ludwig Carl Virchow
(1821-1902) a German physician,
anthropologist, pathologist and statesman,
first coined the term leontiasis ossea in
1864.
It is a historical term used to describe a
number of conditions that result in the
affected patient's face resembling that of
a lion. Although it is most frequently
associated withcraniofacial fibrous
dysplasia and has a broader meaning
encompassing other lesions that have
similar appearance.

4. Robert Kienböck (1871 –1953) was an Austrian
radiologist first mentioned symptomatic forms of
Leotiasis ossea as Osteitis Deformans (Paget’s
Disease) and Osteitis Fibrosa generalisata
(overproduction of Parathyroid glands causing bone
disorders)

5. In 1953
Cohen et al first described the symptoms
of secondary hyperparathyroidism (SHPT)
in chronic renal failure (CRF) as uremic
leontiasis ossea (ULO), which was
characterized by disfiguring facial
deformity due to progressive bony
overgrowth in the craniomaxillofacial
region, resulting in a lion-like face.

6. Secondary Hyperparathyroidism
(SHPT)
Secondary hyperparathyroidism (SHPT) is a long-term complication of chronic kidney
disease–mineral and bone disorder (CKD-MBD).
SHPT is characterized by hyperplasia of the parathyroid glands and abnormal secretion
of parathyroid hormones (PTH), calcium and phosphorous metabolic disorders, renal
osteodystrophy, vascular and soft tissue calcification, malnutrition, and other multiple
system complications, which can seriously affect the quality of life of the patient and
increase the risk of cardiovascular disease and mortality rate.
Uremic leontiasis ossea (ULO) is a medical condition only rarely encountered clinically.

7. Chronic Kidney Disease
CKD is defined as abnormalities of kidney structure or function, present for
>3 months, with implications for health.
CKD requires one of two criteria documented or inferred for >3 months:
either GFR <60 ml/min/1.73 m2 or markers of kidney damage, including
albuminuria, urinary sediment abnormalities.

10. Pathogenesis of Secondary Hyperparathyroidism

11. Definition, evaluation, and classification of renal
osteodystrophy: A position statement from Kidney Disease:
Improving Global Outcomes (KDIGO)
It is recommended that
(1) the term renal osteodystrophy be used exclusively to define alterations in bone
morphology associated with CKD, which can be further assessed by histomorphometry
and the results reported based on a unified classification system that includes
parameters of turnover, mineralization and volume.
(2) the term CKD-Mineral and Bone Disorder (CKD-MBD) be used to describe a
broader clinical syndrome that develops as a systemic disorder of mineral and bone
metabolism due to CKD, which is manifested by abnormalities in bone and mineral
metabolism or extra-skeletal calcification. The international adoption of these
recommendations will greatly enhance communication, facilitate clinical decision-
making and promote the evolution of evidence-based clinical practice guidelines
worldwide.

13. Vit D & PTH role in Calcium homeostasis

15. SHPT & CKD-MBD
The overproduction of parathyroid
hormone are secondary to
hypocalcemia (due to low levels of
Vit D/CKD) cause hyperplaisia of
parathyroid glands leading to
Secondary Hyperparathyroidism.
Sign and symptoms:
Joint/Bone pain
Deformed limbs
Increase IPTH
Loss of Calcium from bones
Vascular/CVD calcification
Neurological symptoms
Muscle weakness
Depression
Psychomotor depression

17. Patient was a 62 yr old Male.
HPI: Patient was under dialysis for 12 years in a county in China. He
had an elevated iPTH levels during the last three years and during
past year was put on calcitriol.
PMH: Hypertension, Chronic Glomerulonephritis on HD
He was referred with iPTH levels of 477 pg/ml
Case: Uremic Leontiasis Ossea

18. Craniofacial deformities
Fracture mid shaft of left
humerus
Chest deformities
Decrease body height
Deformities of bilateral lower
limbs
Case: Uremic Leontiasis Ossea

19. Hb 11.8 g/dl
Urea 23.79 mmol/L
Creatinine 606.1 mmol/L
Calcium 2.78 mmol/L
Phosphate 1.64mmol/L
iPTH 2183.2 pg/mL
ALP 1138.7 U/L
Case: Uremic Leontiasis Ossea

20. Case: Uremic Leontiasis Ossea
Case: Uremic Leontiasis Ossea

21. Case: Uremic Leontiasis Ossea

22. Case: Uremic Leontiasis Ossea

23. 99mTc-MDP bone scintigraphy, whole-
body scan
(A) Anterior
view showed bone thickening mainly in
the mandible, clavicle, sternum
(tie sign) and sacrum.
(B) Posterior view showed bone
thickening mainly
in the scapula, spine and pelvis.
Case: Uremic Leontiasis Ossea

24. Case: Uremic Leontiasis Ossea
Auxillary examination
B-ultrasound
revealed bilateral hypoechoic areas and hyperplasia of the
parathyroid.
Emission Computed Tomography (ECT)
Hyperparathyroid tissue development (left and right sides,
superior and inferior sides of parathyroid glands were
detected on the posterior part of the thyroid gland).

25. What are parathyroid glands?
Parathyroid(PT) glands are 4 small glands
that are located near the thyroid gland in
your neck (size of a pea).
The glands release parathyroid hormone
from chief cells. PT hormones
regulates Ca2+ levels in blood:
A.Bones- PT stimulates release of calcium
from bone into bloodstream.
B.Kidneys- PT hormones reduces loss of
Ca2+ in urine. PT stimulates production of
active Vit D.
C.Intestine- Increase Calcium absorption
from food via Vit D metabolism.

26. Secondary Hyperparathyroidism
(SHPT)
It was postulated that a retention in phosphate in the extracellular space due to
decrease in GFR and decrease plasma Calcium was the primary event for
pathogenesis of SHPT.
However this hypothesis became less attracted when it was demonstrated that
phosphate level was rarely elevated in early stage of CKD.
Its was found that FGF23 a circulating peptide from bone osteocyte controlling
phosphate levels
Both FGF23 and PTH secretion could correct the high plasma phosphate.

27. Fibroblast Growth Factor-23 (FGF23)
Fibroblast Growth Factor-23 (FGF23)
produced by osteocytes and
osteoblasts:
•Decrease tubular reabsorption of
phosphate.
•Is independent of PTH and inhibits
synthesis of PTH
•Decrease renal synthesis of Calcitriol
Drüeke TB. Hyperparathyroidism in
Chronic Kidney Disease.

29. Published in Australian family physician

30. Case: Uremic Leontiasis Ossea

31. KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis,
Evaluation, Prevention, and Treatment of Chronic Kidney Disease–Mineral
and Bone Disorder (CKD-MBD)
Guidelines
In patients with CKD G3a–G5D:
• Treatments of CKD-MBD should be based on serial assessments of phosphate,
calcium, and PTH levels and individualized to patients.
• We suggest avoidance of hypercalcaemia, maintaining serum calcium below the
upper limit of the reference range.

32. KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis,
Evaluation, Prevention, and Treatment of Chronic Kidney Disease–Mineral
and Bone Disorder (CKD-MBD)
Guidelines Phosphate
In patients with CKD G3a–G5D:
• A pragmatic and individualized approach to lowering elevated phosphate
levels toward the normal range.
• Decisions about phosphate-lowering treatment should be based on
progressively or persistently elevated serum phosphate.
• We suggest limiting dietary phosphate intake in the treatment of
hyperphosphatemia alone or in combination with other treatments. It is
reasonable to consider phosphate source (e.g., animal, vegetable, additives)
in making dietary recommendations.

33. KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis,
Evaluation, Prevention, and Treatment of Chronic Kidney Disease–Mineral
and Bone Disorder (CKD-MBD)
Guidelines PTH
In patients with CKD G3a–G5:
1. Patients with levels of intact PTH progressively rising or persistently above
the upper normal limit for the assay be evaluated for modifiable factors,
including hyperphosphatemia, hypocalcemia, high phosphate intake, and
vitamin D deficiency .
2. We suggest that calcitriol and vitamin D analogs not be routinely used. It is
reasonable to reserve the use of calcitriol and vitamin D analogs for patients
with CKD G4–G5 with severe and progressive hyperparathyroidism.

34. KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis,
Evaluation, Prevention, and Treatment of Chronic Kidney Disease–Mineral
and Bone Disorder (CKD-MBD)
Guidelines PTH
3. In patients with CKD G5D requiring PTH-lowering therapy, we suggest
calcimimetics, calcitriol, or vitamin D analogs, or a combination of
calcimimetics with calcitriol or vitamin D analogs.
4. In patients with CKD G3a–G5D with severe hyperparathyroidism (HPT) who
fail to respond to medical or pharmacological therapy, we suggest
parathyroidectomy.

35. Parathyroidectomy with forearm autotransplantation

36. Case: Uremic Leontiasis Ossea

37. Case: Uremic Leontiasis Ossea
Blood
markers
Preoperative Postoperative
Calcium 2.78 mmol/L 2.20 mmol/L
iPTH 2183.2 pg/mL 57.2 pg/mL
Phosphorus 1.64 mmol/L 0.904 mmol/L
ALP 1138.7 U/L 297 U/L

38. Uremic patients often also experience cardiopulmonary insufficiency, vascular
calcification, malnutrition, bleeding during the intraoperative and perioperative periods,
infection, arrhythmia, circulatory disorders, and other complications.
In order to improve the safety and effectiveness of TPTX surgery. Preoperative
parathyroid localization tests include ultrasound and ECT is necessary.
Most people have four parathyroid glands. This patient had five, meaning that he had
one supernumerary parathyroid gland.
The reported rate of supernumerary parathyroid glands is around 2.5% to 13%.
Studies have shown that CKD - SHPT patients undergoing TPTX had an incidence of
ectopic parathyroid glands of about 15%, and these glands are mainly distributed
around the thymus, esophageal tissue, carotid sheath, and mediastinum.
Case: Uremic Leontiasis Ossea

39. ULO is the most dramatic pattern of hyperparathyroidism. Parathyroidectomy is
recommended for patients with severe SHPT refractory to drug therapy.
Presently, guidelines suggest surgical intervention if severe SHPT is persistently
elevated (serum iPTH>800 pg/mL) with hypercalcemia and hyperphosphatemia, and if
the case is resistant to drug treatment.
In conclusion, PTX with autotransplantation is an effective way to treat SHPT caused
by chronic renal failure. It relieves patients from mineral bone disorders, alleviates
vascular calcification, improves bone health and quality of life. However, abnormal
stature caused by vertebral fractures cannot be reversed in cases with excessive
skeletal malformation.
Case: Uremic Leontiasis Ossea