- 1 Definition
- 2 Disease Causes
- 3 Risk Factors
- 4 Symptoms
- 5 Investigations and diagnosis
- 6 Treatment
- 7 Similar diseases/ differential diagnoses
- 8 Guidelines
- 9 Literature
In the case of bone fragility (osteoporosis), there is low bone mass and the construction (architecture) in the bone tissue is weakened. This increases the risk of bone fractures. In the skeleton, a continuous build-up and breakdown of bone tissue takes place. Low bone mass occurs when the breakdown exceeds the build-up over time. Osteoporosis is defined by a DEXA measurement shows "T-score" for bone density/bone mass of -2,5 or lower. In the case of "severe osteoporosis", there must also be osteoporotic fractures. Osteopenia implies a T-score between -1.0 and -2.5 (between normal bone density and osteoporosis). Among children, osteoporosis is defined by comparing the bone mass with what is normal for the corresponding age ("Z-score"). Gestational osteoporosis is related to pregnancy and lactation which can affect otherwise healthy women in the latter part of pregnancy or during the breastfeeding period. Osteoporosis leads to reduced quality of life, reduced health, disability and increased mortality (Matthew A, 2014). Osteoporosis is separated osteopenia which is a precursor (see more below), and from osteomalacia which is limited to reduced mineralization (most often storage of calcium) in the skeleton.
White European and North American women have the highest fracture risk due to osteoporosis. Asian and African-American women have the lowest risk. Hip fracture in the mother predisposes to osteoporosis.
Primary osteoporosis can be divided into postmenopausal osteoporosis (loss of estrogen after menopause is the most common cause), age-related osteoporosis (caused by an imbalance between calcium and vitamin D leading to secondary hyperparathyroidism) and idiopathic osteoporosis.
Secondary osteoporosis due to several causes: Cortisone-induced (for example with prednisolone) osteoporosis) is due to a reduced imbalance between building up and breaking down of the skeleton (osteoblast and osteoclast activity). A number of diseases are predisposing factors: Hormonal (endocrine) diseases as primary hyperparathyroidism, endogenous cushing syndrome and high metabolism / thyrotoxicosis, rheumatic diseases (arthritis/RA, Bekhterev's (ankylosing spondylitis), intestinal diseases (reduced absorption) in celiac disease and Crohn's, kidney failure, chronic liver disease, alcoholism, chronic lung disease and cancer (for example multiple myeloma).
In the case of rheumatic diseases, there is particular cortisone treatment prednisolone which can lead to osteoporosis. Especially older women (estrogen deficiency) have an increased risk.
Gestation osteoporosis is due to a combination of several factors. During pregnancy, the development of the fetus's skeleton requires that large amounts of calcium (limestone) be transferred from the pregnant woman's skeleton. Milk production during breastfeeding depletes the woman of calcium in addition to the fact that estrogen is low. It is estimated that women have a 4-6% loss of bone mass in the first 6 months when breastfeeding (reference: Hopkinson JM, 2000). It is still unclear why some women develop severe osteoporosis related to pregnancy, but some are predisposing: Genetic (hereditary) predisposition, lack of calcium and Vitamin D, use of Heparin (blood thinner) and low body weight.
- Age. An 80-year-old woman has approximately 25 times greater risk of hip fracture than a 55-year-old.
- Hyperparathyroidism (high calcium and high PTH (parathyroid hormone) in the blood
- Sex. Women have almost double the risk of hip fracture compared to men.
- Cholesterol-lowering drugs (statins) can increase the risk of osteoporosis, but this has only been shown for high doses. It is unclear whether the cause is the drug or that lower cholesterol is associated with an increased risk of osteoporosis (reference: Leutner M, 2019)
- Cortisone use (prednisolone) over a long period of time is a significant risk factor, especially for people with rheumatic disease.
- Diet with low intake of Calcium and D vitamins
- Low body weight
- Little physical activity
- Low sun exposure (low Vitamin D)
- Proton pump inhibitors (long-term use against stomach acid-related symptoms). Absorption of nutrients such as calcium and magnesium is reduced (Raknes G, 2020)
- Metabolic disease (hyperthyroidism)
- Pregnancy and breastfeeding (Pregnancy Osteoporosis)
- Reduced intestinal uptake (for example in intestinal disorders)
- Smoking and high alcohol consumption
Osteoporosis causes no symptoms until a fracture occurs.
Osteoporosis fractures are most often painful and can occur almost spontaneously. Break in vertebrae (compression fracture), fractures in the wrist, femoral neck, ribs and in other parts of the skeleton, even with little strain or injury, are typical. The pain gets worse with almost any kind of movement. The symptoms last from 4-6 weeks to several months. After each, one becomes pain-free, but the X-ray changes are permanent. As a result of collapsing in the back (compression fractures), the back often becomes curved and body height decreases. It is unusual for nerve roots and the spinal cord to be compressed by osteoporotic fractures.
Investigations and diagnosis
Osteoporosis is usually detected by bone density / bone mass measurement. The measurement uses a small dose of X-rays, called dual energy X-ray absorptiometry (DEXA measurement). The result provides good evidence for future breach risk. Many rheumatic and x-ray departments have such machines and receive referrals from GPs / GPs.
Interpretation of measurement values at DEXA
- T-score -1,0 or higher indicates normal bone density
- Osteopenia is a precursor to osteoporosis where T-scores between -1,0 and -2,5
- Osteoporosis is defined by T-score -2,5 or less
- Z-scores are also often given and show the bone density in percentage (%) compared to results from healthy people in the same age group and sex.
- Although bone mass usually correlates well with fracture risk, the measurement values do not show how the architecture of the bone substance is. A weak bone structure can occur even if bone density/bone mass is good.
- Some DEXA machines can also take side images of the spine to detect compression fractures with overlapping vertebrae.
- Control measurement of bone density is often done after approx. 2 years to see if there is improvement after treatment or development for the worse and then an indication for supplementary treatment.
Bone markers for the formation of new bone tissue
Bone markers measure the formation of new bone tissue (P1NP) or breakdown (CTX-1). Both are usually elevated with high bone turnover, such as with osteoporosis, growing children, active rheumatic inflammation, after major fractures, menopause, hyperparathyroidism, reduced kidney function and Paget's disease (rare condition). Bone markers are particularly relevant if the treatment does not work as expected, or if you want to follow up the effect of bisphosphonates (antiresorptive treatment). It is then best if the bone marker P1NP (see below) is measured before starting treatment and after 3-6 months. Bone markers are not suitable for screening or diagnosing osteoporosis. Please note that treatment with corticosteroids (prednisolone) can give falsely low values (Borgen TT, 2021).
- N-terminal Propeptide of Collagen Type I (PINP) is considered the best marker. Reference values: Postmenopausal woman 16-96 mcg/L, Premenopausal woman 19-83 mcg/L, Adult man 22-87 mcg/L.
- PINP should be measured before starting treatment and after 6 months. An increase of 21% or more indicates a treatment effect. The P1NP concentration is expected to fall by 50% within 3-6 months after starting treatment with bisphosphonates, estrogens, SERMs and RANKL inhibitors and should be in Lower part of the reference area during the treatment period. After starting up anabolic drugs is expected that after 1 months P6NP is i upper the reference range, that is >60,9 mcg/L.
- The correct length of treatment break with bisphosphonates can be estimated by P1NP. An increase of over 30% or to or values > 35 mcg/L indicates increasing bone turnover with new osteoporosis development which may be an indication for re-starting bisphosphonate.
- PINP is not suitable for screening or diagnosis of osteoporosis
- In severe hepatic disease, the test can not be used (metabolism of PINP through liver)
- CTX-1 (carboxy-terminal telopeptide from type 1 collagen) is a marker for osteoclast activity (breakdown of bone substance), but is not stable and more difficult to interpret because it has diurnal variations (sampling in the morning) and is affected by food intake (fasting sample).
Other blood samples that can be taken in the investigation of osteoporosis
- Lowering reaction (SR), CRP, hemoglobin (Hgb), white blood cells (leukocytes), platelets (platelets), calcium, albumin, creatinine, ALAT, alkaline phosphatase (ALP), TSH, 25 (OH) vitamin D, phosphate, parathyroid hormone ( PTH) and electrophoresis. Testosterone in men.
- In osteomalacia (weak bone substance) there is elevated alkaline phosphatase (almost all), low calcium in blood and urine (>90%). Low 25(OH) vit D (<15 ng/mL) in almost everyone.
Preventive measures should be carried out among people with significant risk factors. Threshold to do measurement of bone density should also be low. At the same time as long-term use of prednisolone or other cortisone preparations should Calcium and Vitamin D (eg Calcigran Forte chewable tablets 1000 mg / day or Kalcipos which can be swallowed). In the case of conspicuously low bone mass, it is often supplemented with alendronate or another bisphosphonate for a period of time. First, risk factors are reduced as far as possible:
- Reduce possible cortisone dose (prednisolone)
- Custom physical activity
- Sun exposure (increases vitamin D)
- Calcium and vitamin D (for example Calcigran Forte 1000mg / day)
Medicines which reduce the breakdown of bone mass (anti-resorptive drugs). Everyone is recommended to read up on the use of these medicines. Patient information has been prepared by the Norwegian Rheumatological Association/Medical Association.
bisphosphonates, for example Alendronate tablets makes taken on an empty stomach with water, as described in the package insert. Otherwise, the treatment has no effect. If you have been unlucky enough to have already had an osteoporosis fracture, correct use will reduce the risk of new fractures by 40-70%. Bisphosphonate can alternatively be given intravenously, for example with zoledronate (Alclasta) 5 mg IV once a year. A disadvantage is that some people get a febrile reaction after the infusion. Seizures of chondrocalcinosis occurs after intravenous treatment. Too low calcium in the blood occurs and should be checked before treatment. Pain in joints and muscles is also a possible side effect. If bisphosphonates have been used for longer than 5 years, the indication must be carefully assessed again. Damage to bone tissue in the jaws and drug-related bone fractures are very rare side effects, most often with large drug doses. Often, the bone mass remains for several years after the end of treatment, otherwise it is changed to another type of treatment (please see below). If osteoporosis fractures occur during alendonate treatment, bone mass-building (anabolic), PTH-analog drugs are appropriate.
Denosumab (Prolia) (RANKL inhibitor) 60 mg subcutaneously every 6 months in case of lack of effect and/or unacceptable side effects of oral bisphosphonate or renal failure (eGFR < 30 ml/min). Continuous use, but benefit-risk is assessed especially for 5 years or more. Calcium in the blood may become low and should be checked.
SERMs (Estrogen receptor regulating substances), Evista (raloxifene) pills. Used for women 45-60 years of age.
Romosozumab (Evenity) injections monthly for one year to postmenopausal women with severe osteoporosis. Current in severe cases with T-score < -4,0, multiple fractures (3 or more back fractures at the time of diagnosis), severe back fractures (SQ3 fracture > 40% compression), or in case of a new fracture during ongoing bisphosphonate treatment.
Teriparatide (Forsteo) (PTH analogue) 20 µg subcutaneous x 1 daily for 2 years is the first-choice preparation in severe cases with a T-score ≤ -3,5, multiple fractures (3 or more back fractures at the time of diagnosis), severe back fractures (SQ3 fracture > 40% compression), or in case of a new fracture during ongoing bisphosphonate treatment. Excessive calcium in the blood and the development of kidney stones may occur during treatment. The treatment must not be given in the case of cancer where there may be metastases to the skeleton.
Testosteron can be used for osteoporosis in men where there is a hormone deficiency. Nebido 1000 mg IM injection every 3 months or testosterone gel percutaneous daily.
Similar diseases/ differential diagnoses
- Malignant diseases in the skeleton: primary tumors and metastases.
- Methotrexate osteopathy. Stress fracture-like non-traumatic injuries, most often in the lower extremities. Distal tibia is attacked os >50%, calcaneus 35% and proximal tibia 28%. The condition is very rare, but is recognized by typical MRI findings with band-shaped defects such as growth zone changes (Ruffer N, 2022).
- Multiple myeloma / multiple myeloma
- Osteomalacia (among adults) and rickets (in children). Lack of calcium and other mineralization of the skeleton. Causes are most often a lack of Vitamin D (too low intake), calcium and / or phosphate. Brings "soft bones". May overlap with osteoporosis, but bone mass need not be reduced. Medical examinations: Measurement of 25(OH)vitamin D, calcium, phosphate, parathyroid hormone (PTH), alkaline phosphatase and creatinine (kidney function).
- Osteopenia. Low bone mass (T-score between -1,0 and -2,5).
- Osteitis fibrosis cystica. Loss of bone mass and skeletal structure changes. Caused by hyperparathyroidism. In blood tests, parathyroid hormone, often also calcium and alkaline phosphatase are elevated.
- Osteopetrosis. Forum high bone density. Rare, hereditary disease. Alkaline phosphatase is elevated in a blood test.
- Paget's disease (Osteitis deformans). Adults (over 55 years of age), mostly men. bone pain. Gradual remodeling and thickening of the skeleton, mostly in the pelvis, thighs, vertebrae and skull. Blood alkaline phosphatase is often elevated.
- Sickle cell anemia
- Porter JL, 2022
- Kanis JA, 2012 (Diagnosis and Management)
- Norwegian supervisor (endocrinology)
- Grans Compendium in Rheumatology