Oxalic acid has a very strong affinity for calcium, forming calcium oxalate—a salt that is highly insoluble in water. The solubility product constant (Ksp) for calcium oxalate monohydrate is around 2.3 × 10⁻⁹, indicating that even small amounts of oxalic acid and calcium ions in solution will readily precipitate out as crystals. This high affinity is a major reason calcium oxalate is the most common component of kidney stones and why oxalate tends to deposit in tissues when calcium is present and oxalate clearance is impaired.
Calcium is normally present in several tissues, primarily where it plays structural or regulatory roles. About 99% of the body’s calcium is stored in bones and teeth, providing strength and rigidity. The remaining 1% is found in soft tissues and body fluids, where it supports critical functions. Normal soft tissue reservoirs include:
-Blood plasma and interstitial fluid (as ionized calcium and bound forms)
-Muscle tissue (especially within the sarcoplasmic reticulum, regulating contraction)
-Nerve tissue (for neurotransmitter release)
-Endocrine tissues (e.g., parathyroid glands for calcium sensing)
-Mitochondria (in many cells, where calcium regulates metabolism)
Calcium is essential, but its accumulation outside controlled compartments (e.g., as crystals in soft tissues) is abnormal.
There are dozens of distinct disorders—genetic, metabolic, infectious, autoimmune, and toxic—that can lead to soft tissue calcification throughout the body. These fall broadly into two categories: dystrophic calcification (where calcium deposits in damaged tissues despite normal blood calcium levels) and metastatic calcification (from elevated calcium/phosphate levels). Examples include:
-Chronic kidney disease
-Hyperparathyroidism
-Sarcoidosis
-Systemic sclerosis
-Dermatomyositis
-Tumoral calcinosis
-Idiopathic basal ganglia calcification
-Calciphylaxis
-Vitamin D toxicity
-Mitochondrial disorders
-Genetic phosphate metabolism disorders (e.g., ENPP1, ABCC6 mutations)
The actual number of recognized conditions likely exceeds 50, with overlapping mechanisms involving phosphate dysregulation, tissue damage, or crystal deposition.
Soft tissue calcification can result from a wide array of disorders, encompassing genetic, metabolic, autoimmune, infectious, neoplastic, and iatrogenic causes. These conditions can affect various body regions, including muscles, skin, joints, internal organs, glands, and brain tissues. Below is an extensive list of over 50 disorders and conditions associated with soft tissue calcification:
1. Genetic and Hereditary Disorders
-Pseudoxanthoma Elasticum (PXE)
-Generalized Arterial Calcification of Infancy (GACI)
-Arterial Calcification due to Deficiency of CD73 (ACDC)
-Fibrodysplasia Ossificans Progressiva (FOP)
-Osteogenesis Imperfecta
-Ehlers-Danlos Syndrome
-Marfan Syndrome
-Loeys-Dietz Syndrome
-Alkaptonuria
-Mucopolysaccharidoses (e.g., Hurler, Hunter syndromes)
-Primary Familial Brain Calcification (Fahr’s Disease)
-Idiopathic Basal Ganglia Calcification
-Congenital Contractural Arachnodactyly (Beals Syndrome)
-Stickler Syndrome
-Hypermobility Spectrum Disorders
2. Metabolic and Endocrine Disorders
-Chronic Kidney Disease (CKD)
-Secondary Hyperparathyroidism
-Primary Hyperparathyroidism
-Vitamin D Toxicity
-Milk-Alkali Syndrome
-Tumoral Calcinosis
-Hyperphosphatemia
-Hypophosphatasia
-Diabetes Mellitus (leading to Mönckeberg’s Arteriosclerosis)
-Wilson’s Disease
3. Autoimmune and Connective Tissue Diseases
-Systemic Sclerosis (Scleroderma)
-Dermatomyositis
-Polymyositis
-Systemic Lupus Erythematosus (SLE)
-Mixed Connective Tissue Disease (MCTD)
-Rheumatoid Arthritis
-Sjögren’s Syndrome
-CREST Syndrome (a subset of systemic sclerosis)
4. Infectious Diseases
-Cysticercosis
-Tuberculosis (leading to caseous necrosis and calcification)
-Congenital Toxoplasmosis
-Cytomegalovirus (CMV) Infection
-Rubella
-Schistosomiasis
5. Neoplastic Conditions
-Osteosarcoma (primary or metastatic)
-Synovial Osteochondromatosis
-Calcifying Epithelial Odontogenic Tumor
-Pilomatricoma
-Calcifying Fibrous Tumor
6. Vascular and Cardiovascular Disorders
-Atherosclerosis
-Monckeberg’s Arteriosclerosis
-Calciphylaxis
-Chronic Venous Insufficiency
-Phleboliths (calcified venous thrombi)
7. Neurological Disorders
-Primary Familial Brain Calcification (Fahr’s Disease)
-Idiopathic Basal Ganglia Calcification
-Neurocysticercosis
8. Trauma and Iatrogenic Causes
-Myositis Ossificans (post-traumatic)
-Heterotopic Ossification (post-surgical or post-injury)
-Injection Granulomas
-Iatrogenic Calcinosis Cutis (e.g., from calcium-containing IV infusions)
9. Idiopathic and Miscellaneous Conditions
-Idiopathic Scrotal Calcinosis
-Subepidermal Calcified Nodule
-Osteoma Cutis
-Calcific Tendinitis
-Diffuse Idiopathic Skeletal Hyperostosis (DISH)
-Calcinosis Cutis (various subtypes)
This compilation underscores the diverse etiologies and systemic nature of soft tissue calcification.