{"id":9057,"date":"2021-12-11T19:42:43","date_gmt":"2021-12-11T17:42:43","guid":{"rendered":"https:\/\/meddists.com\/learn\/clinical\/rheumatology\/disorders-of-bone-metabolism-and-bone-turnover-osteoporosis-pagets-disease-osteomalacia-osteonecrosis\/"},"modified":"2022-04-24T13:53:08","modified_gmt":"2022-04-24T11:53:08","slug":"disorders-of-bone-metabolism-and-bone-turnover-osteoporosis-pagets-disease-osteomalacia-osteonecrosis","status":"publish","type":"page","link":"https:\/\/meddists.com\/learn\/clinical\/internal-medicine\/rheumatology\/disorders-of-bone-metabolism-and-bone-turnover-osteoporosis-pagets-disease-osteomalacia-osteonecrosis\/","title":{"rendered":"Disorders of bone metabolism and bone turnover: osteoporosis, Paget\u2019s disease, osteomalacia, osteonecrosis"},"content":{"rendered":"<span class=\"block-heading\" id=\"header_1\">\n<h3 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title1\">Osteoporosis<\/h3>\n<\/span><span class=\"block-content\" id=\"contents_1\">\n\n<\/span><span class=\"block-heading\" id=\"header_2\">\n<h4 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title2\">Introduction<\/h4>\n<\/span><span class=\"block-content\" id=\"contents_2\">\n\n\n<ul class=\"wp-block-list\"><li><strong>Peak bone mass&nbsp;<\/strong>is influenced by several factors such as genetics, environment, physical activity, and nutrition<\/li><li>Post-adulthood (over the age of 25-30), our bone mass starts to decreases by 0.7% each year, on average<\/li><li><strong>Osteopenia<\/strong>&nbsp;is an abnormal decrease in bone mass<\/li><li><strong>Osteoporosis<\/strong>&nbsp;(literally, the formation of pores in the bone) a&nbsp;severe&nbsp;decrease in bone mass<\/li><\/ul>\n\n\n\n<p class=\"wp-block-paragraph\">Clinically, mineral bone mass is determined using a DXA scan. The generated results are reported as T-score and Z-score.<\/p>\n\n\n\n<ul class=\"wp-block-list\"><li>T-score is the number of SD the bone mass of the patient differs from that of a <strong>young, healthy patient<\/strong>. <ul><li>T-score between -1.0 and -2.5 suggests osteopenia<\/li><li>T-score below -2.5 suggests osteoporosis<\/li><\/ul><\/li><li>Z-score is the number of SD the bone mass of the patient differs from that of a <strong>healthy patient of the same age and sex<\/strong>.<\/li><\/ul>\n\n\n<\/span><span class=\"block-heading\" id=\"header_3\">\n<h4 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title2\">Description<\/h4>\n<\/span><span class=\"block-content\" id=\"contents_3\">\n\n\n<p class=\"wp-block-paragraph\">Osteoporosis is a progressive disease of bones in which bone mass decreases. The bones become fragile and fracture easily (these fractures are known as <strong>fragility fractures<\/strong>).<\/p>\n\n\n\n<ul class=\"wp-block-list\"><li>The most common fracture sites are the distal radius, spine (compression fractures), and femoral neck.<\/li><li>More common in older women.<\/li><li><strong>Etiology<\/strong><ul><li><strong>Primary <\/strong>(most common)<ul><li><strong>Aging<\/strong> (senile osteoporosis). Occurs due to the reduced proliferation and activity of osteoblasts,&nbsp;<strong>low-turnover osteoporosis<\/strong>.<\/li><li><strong>Post-menopausal<\/strong>. Occurs as a result of the reduction in estrogen production, leading to an increase in bone resorption, and a smaller increase in bone production &#8211; net bone loss,&nbsp;<strong>high-turnover osteoporosis<\/strong>.<\/li><\/ul><\/li><\/ul><ul><li><strong>Secondary<\/strong><ul><li>Endocrine (hyperthyroidism, hyperparathyroidism, hypogonadism, corticosteroids)<\/li><li>Gastrointestinal (malnutrition, malabsorption)<\/li><li>Malignancies (multiple myeloma)<\/li><\/ul><\/li><\/ul><\/li><li><strong>Morphology and clinical presentation<\/strong><ul><li>The bones become much more susceptible to fractures<ul><li>Vertebral fractures are the most common and give the typical \u201dhunched\u201d appearance in the elderly due to excessive kyphosis<\/li><\/ul><\/li><li>The ratio of osteoid to mineralized bone is normal in individuals with osteoporosis<\/li><li>Histologically, a decrease in cortical thickness and medullary trabeculae is seen<\/li><\/ul><\/li><li><strong>Diagnosis<\/strong><ul><li>Blood panel<\/li><li>Endocrine tests<\/li><li>DXA scan (dual x-ray absorptiometry)<\/li><li>X-ray (fractures)<\/li><\/ul><\/li><li><strong>Treatment<\/strong><ul><li>Exercise and active lifestyle<\/li><li>Calcium (1g\/day) and vitamin D (600IU\/day) supplementation<\/li><\/ul><ul><li>Bisphosphonates (zoledronic acid\/alendronate\/risedronate)<ul><li>Depending on the formulation, can be PO or IV<\/li><li>When taken PO should not eat\/drink anything for 30min after administration<\/li><li>Long-term usage increases the risk for atypical femoral fractures<\/li><li>Not for use in advanced CKD<\/li><\/ul><\/li><li>Estrogen (post-menopausal women)<\/li><li>Denosumab (monoclonal antibody against RANKL)<\/li><li>Romosozumab&nbsp;(monoclonal antibody against sclerostin)<\/li><\/ul><\/li><\/ul>\n\n\n<\/span><span class=\"block-heading\" id=\"header_4\">\n<h3 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title1\">Osteomalacia<\/h3>\n<\/span><span class=\"block-content\" id=\"contents_4\">\n\n\n<p class=\"wp-block-paragraph\">Osteomalacia is a disorder of bones in which the mineralized proportion of the bone is decreased, caused due to vitamin D deficiency, or defects in its metabolism.<\/p>\n\n\n\n<ul class=\"wp-block-list\"><li>Presents with muscle and bone pain, and weakness. Hypocalcemia may lead to tetani.<\/li><li>In children (before the epiphyseal plates are fused), the condition is known as <strong>rickets<\/strong>. <ul><li>Growth retardation<\/li><li>In infants, soft skull (craniotabes), the head feels &#8220;squishy&#8221;<\/li><li>Bowing of the legs<\/li><\/ul><\/li><li><strong>Etiology<\/strong><ul><li><strong>Inadequate exposure to sunlight<\/strong> (Nordic countries)<\/li><li><strong>Inadequate intake of vitamin D<\/strong>. Improper diet.<\/li><li><strong>Malabsorption<\/strong>. Vitamin D is lipid-soluble.<\/li><li><strong>Abnormal vitamin D metabolism<\/strong>. Type I hereditary rickets; defective conversion to the active form.<\/li><li><strong>Resistance to vitamin D<\/strong>. Type II hereditary rickets; defective receptor<\/li><\/ul><\/li><li><strong>Diagnosis<\/strong><ul><li>Serum vitamin D levels<\/li><li>X-ray (bones become radiolucent; first evident in the distal radius and ulna)<\/li><\/ul><\/li><li><strong>Treatment<\/strong>. Vitamin D3, calcium, and phosphate supplementation.<\/li><\/ul>\n\n\n<\/span><span class=\"block-heading\" id=\"header_5\">\n<h4 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title2\">Pathophysiology<\/h4>\n<\/span><span class=\"block-content\" id=\"contents_5\">\n\n\n<p class=\"wp-block-paragraph\">Vitamin D is required for maintaining appropriate serum calcium and phosphate levels, as well as suppressing PTH release.<\/p>\n\n\n\n<ul class=\"wp-block-list\"><li>Its deficiency leads to hypocalcemia, hypophosphatemia, and release of PTH (secondary hyperparathyroidism).<\/li><li>Elevated PTH levels lead to increased calcium absorption and reabsorption from the GI, kidney, and most importantly, bones, while causing urinary phosphate excretion, further excrabating the hypophosphatemia.<\/li><li>Serum calcium levels may seem normal, but the bones lose both calcium and phosphate; this condition is known as <strong>osteomalacia.<\/strong><\/li><\/ul>\n\n\n<\/span><span class=\"block-heading\" id=\"header_6\">\n<h3 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title1\">Paget&#8217;s disease<\/h3>\n<\/span><span class=\"block-content\" id=\"contents_6\">\n\n\n<p class=\"wp-block-paragraph\">Paget&#8217;s disease (<em>osteitis deformans<\/em>) is a pathology of the bones involving bone breakdown followed by a disordered pattern of excessive bone growth.<\/p>\n\n\n<\/span><span class=\"block-heading\" id=\"header_7\">\n<h4 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title2\">Characteristics<\/h4>\n<\/span><span class=\"block-content\" id=\"contents_7\">\n\n\n<ul class=\"wp-block-list\"><li>May affect multiple bones (polyostotic), or a single bone (monostotic, rare); does not involve the entire skeleton.<\/li><li>Bones most commonly affected are the skull, pelvis, and femur.<\/li><li>10% of patients present with a SQSTM1 gene mutation, increasing NF-\u03baB activity which stimulates osteoclast activity.<\/li><li>The cause is thought to be related to a viral infection (measles).<\/li><li>More common in Caucasians, typically in older adults.<\/li><li>Increased risk for tumor development; <strong>secondary osteosarcomas<\/strong>.<\/li><li><strong>Diagnosis<\/strong><ul><li>X-ray<\/li><li>Serum AP (elevated), calcium (elevated), GGT (normal)<\/li><li>Bone scintigraphy<\/li><\/ul><\/li><li><strong>Treatment<\/strong>. Calcitonin and bisphosphonates.<\/li><\/ul>\n\n\n<\/span><span class=\"block-heading\" id=\"header_8\">\n<h4 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title2\">Phases<\/h4>\n<\/span><span class=\"block-content\" id=\"contents_8\">\n\n\n<p class=\"wp-block-paragraph\"> Paget&#8217;s disease progresses in 3 consecutive phases:<\/p>\n\n\n\n<ol class=\"wp-block-list\"><li><strong>Osteolytic phase<\/strong>. Osteoclasts activate without control and break down the bone<ul><li>Histologic sections show giant-cell osteoclasts (100 or more nuclei)<\/li><\/ul><\/li><li><strong>Mixed-phase<\/strong>. Osteoblasts activate in an attempt to reconstruct the bone, and they do so excessively, and in a disordered pattern.<\/li><li><strong>Osteosclerotic phase<\/strong>. Osteoclast &#8220;burnout&#8221;, osteoblast activity&nbsp;continues for some time afterward<\/li><\/ol>\n\n\n<\/span><span class=\"block-heading\" id=\"header_9\">\n<h4 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title2\">Appearance and symptoms<\/h4>\n<\/span><span class=\"block-content\" id=\"contents_9\">\n\n\n<p class=\"wp-block-paragraph\">Paget&#8217;s disease is typically asymptomatic. The bone will appear large, heavy, and deformed, but more fragile.<\/p>\n\n\n\n<ul class=\"wp-block-list\"><li>Depending on the location of involvement, it may cause pain, movement restriction, and displacement of nearby soft tissue<ul><li>The pain is caused by microfractures or compression of spinal nerves<\/li><li>If it appears inside the skull base (<strong>platybasia<\/strong>) it may cause compression of the posterior fossa<\/li><\/ul><\/li><li>The typical facial involvement at the late stage is known as &#8220;<strong>lion face<\/strong>&#8221; (<em>leontiasis ossea<\/em>) due to facial bone deformities.<\/li><li>The fragile bone tends to fracture more easily and damages nearby tissues (vertebral fracture which may lead to spinal cord injury)<\/li><\/ul>\n\n\n<\/span><span class=\"block-heading\" id=\"header_10\">\n<h3 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title1\">Osteonecrosis<\/h3>\n<\/span><span class=\"block-content\" id=\"contents_10\">\n\n\n<p class=\"wp-block-paragraph\">Osteonecrosis (also known as <strong>avascular<\/strong>, <strong>ischemic<\/strong>, or<strong> aseptic necrosis of the bone<\/strong>) is a condition in which bone tissue loses blood supply and becomes infarcted.<\/p>\n\n\n\n<ul class=\"wp-block-list\"><li>Presents with pain, limited ROM<\/li><li>Typically affects the ends of long bones (head of the femur and humerus).<\/li><li>Depending on the severity of the infarct, the bone may either eventually recover, or collapse.<\/li><li>Osteonecrosis of the jaw is associated with bisphosphonates and denosumab usage (against osteoporosis).<\/li><li><strong>Etiology<\/strong>. Osteonecrosis most commonly occurs due to trauma, but it may also be due to other causes, such as:<ul><li>Endocrinology (corticosteroids, DM)<\/li><li>Alcoholism<\/li><li>Infections<\/li><li>Vasculitis<\/li><li>Sickle-cell anemia <\/li><\/ul><\/li><li><strong>Diagnosis<\/strong>. Radiological imaging.<\/li><li><strong>Classification<\/strong>. The <strong>Ficat<\/strong> classification system describes the severity by 4 stages based on the radiological findings.<\/li><li><strong>Treatment<\/strong> <ul><li>Load reduction and rest<\/li><li>NSAIDs and analgesics<\/li><li>Bisphosphonates (limited evidence)<\/li><li>Surgery (reduce edema in early stages; joint replacement in late)<\/li><\/ul><\/li><\/ul>\n\n\n<\/span><span class=\"block-heading\" id=\"header_11\">\n<h4 class=\"wp-block-heading\" class=\"wp-block-heading\" class=\"title_collection title2\">Distinct forms<\/h4>\n<\/span><span class=\"block-content\" id=\"contents_11\">\n\n\n<p class=\"wp-block-paragraph\">There are several distinct forms of osteonecrosis:<\/p>\n\n\n\n<ul class=\"wp-block-list\"><li><strong>Perthes disease.<\/strong> Necrosis of the femoral head, appearing between ages 4-10<\/li><li><strong>Osgood-Schlatter disease<\/strong>. Necrosis of the tibial tuberosity, appearing between ages 10-16<\/li><li><strong>Kienb\u00f6ck\u02bcs disease<\/strong>. Necrosis of the lunate of the hand.<\/li><li><strong>K\u00f6hler disease<\/strong>. Necrosis of the navicular and 2nd metatarsal bone.<\/li><\/ul>\n<\/span><div id=\"the_titles\" style=\"display:none;\"><h3 class=\"wp-block-heading\" class=\"wp-block-heading\">Osteoporosis<\/h3><h4 class=\"wp-block-heading\" class=\"wp-block-heading\">Introduction<\/h4><h4 class=\"wp-block-heading\" class=\"wp-block-heading\">Description<\/h4><h3 class=\"wp-block-heading\" class=\"wp-block-heading\">Osteomalacia<\/h3><h4 class=\"wp-block-heading\" class=\"wp-block-heading\">Pathophysiology<\/h4><h3 class=\"wp-block-heading\" class=\"wp-block-heading\">Paget&#8217;s disease<\/h3><h4 class=\"wp-block-heading\" class=\"wp-block-heading\">Characteristics<\/h4><h4 class=\"wp-block-heading\" class=\"wp-block-heading\">Phases<\/h4><h4 class=\"wp-block-heading\" class=\"wp-block-heading\">Appearance and symptoms<\/h4><h3 class=\"wp-block-heading\" class=\"wp-block-heading\">Osteonecrosis<\/h3><h4 class=\"wp-block-heading\" class=\"wp-block-heading\">Distinct forms<\/h4><\/div>","protected":false},"excerpt":{"rendered":"<p>Osteoporosis Introduction Peak bone mass&nbsp;is influenced by several factors such as genetics, environment, physical activity, and nutrition Post-adulthood (over the age of 25-30), our bone mass starts to decreases by 0.7% each year, on average Osteopenia&nbsp;is an abnormal decrease in bone mass Osteoporosis&nbsp;(literally, the formation of pores in the bone) a&nbsp;severe&nbsp;decrease in bone mass Clinically, [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"parent":8424,"menu_order":9,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"class_list":["post-9057","page","type-page","status-publish","hentry"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.9 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Disorders of bone metabolism and bone turnover: osteoporosis, Paget\u2019s disease, osteomalacia, osteonecrosis &#8211; 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