Arthritis, Osteoporosis, and Back Pain

TL;DR. These are the diseases of the body's structure, and they cause more disability worldwide than anything else. Osteoarthritis is not simply wear and tear; it is a failing repair process in the whole joint, and the pain correlates poorly with what the X-ray shows. Osteoporosis is silent bone loss that announces itself only when something breaks, and a hip fracture at 80 carries a mortality comparable to many cancers. Gout is uric acid crystallising inside a joint, one of the few forms of arthritis that is genuinely curable and one of the worst treated. Low back pain is the single leading cause of years lived with disability on earth, and most of what has traditionally been done for it (scans, rest, opioids, and a great deal of surgery) makes it worse rather than better.

Key takeaways

• Low back pain is the world's leading cause of disability, affecting around 600 million people, and over 90 percent of cases have no identifiable structural cause.
• Imaging findings are not diagnoses. Disc degeneration appears on MRI in the majority of people over 40 who have no pain at all, and the same disconnect holds for knee osteoarthritis.
• Exercise is the best-evidenced treatment for both osteoarthritis and back pain, and it outperforms most drugs and many procedures.
• Osteoporotic fracture is common and treatable, and treatment rates are appalling: the majority of people who suffer a fragility fracture are never assessed or treated for the underlying bone disease.
• Gout is curable in the sense that lowering uric acid below a target dissolves the crystals and stops the attacks permanently. Most patients are treated only for their attacks.
• A hip fracture kills roughly 20 to 30 percent of older patients within a year, and most survivors never regain their previous independence.

Osteoarthritis

In short: Not simple wear and tear but a failing repair process, and the pain correlates poorly with what the X-ray shows because cartilage has no nerves.

What it is. A disease of the whole joint: cartilage breaks down, the underlying bone thickens and forms spurs (osteophytes), the joint lining becomes mildly inflamed, and ligaments and muscles around the joint weaken. It most commonly affects knees, hips, hands, and the spine.

What actually goes wrong. Cartilage has no blood supply and no nerves, and its cells (chondrocytes) maintain a matrix of collagen and proteoglycans that gives it its compressive strength and slipperiness. In osteoarthritis, mechanical stress and inflammatory signals push chondrocytes into a degradative state: they produce enzymes (matrix metalloproteinases, aggrecanases) that break down the matrix faster than it can be rebuilt. This is an active, regulated process rather than passive erosion, which is why "wear and tear" is a misleading description and why joint loading through appropriate exercise helps rather than hastens it.

Because cartilage itself has no nerves, the pain does not come from the cartilage. It comes from the bone underneath (which develops microfractures and lesions visible on MRI), the joint lining, the capsule, and surrounding structures, plus central pain sensitisation in longstanding cases. This is the mechanism behind one of the most important facts in musculoskeletal medicine: radiographic severity and pain correlate weakly. Plenty of people have severe changes on X-ray and no symptoms, and plenty have disabling pain with modest changes.

Who gets it. Age (the dominant factor), female sex after menopause, obesity (which acts both mechanically and metabolically, which is why obesity also increases hand osteoarthritis where load is irrelevant), previous joint injury (an anterior cruciate ligament rupture raises knee osteoarthritis risk enormously), occupational loading, and genetics, which account for roughly 40 to 65 percent of risk depending on the joint.

Treatment, in order of evidence:

1. Exercise. Strengthening and aerobic exercise reduce pain and improve function in knee and hip osteoarthritis, with effect sizes comparable to non-steroidal anti-inflammatories. It has to be sustained; the benefit fades when it stops.
2. Weight loss where relevant. Losing 10 percent of body weight produces clinically meaningful improvement in knee pain, partly through load and partly through reduced inflammatory signalling.
3. Topical NSAIDs, which are effective for knee and hand osteoarthritis with far lower systemic risk than tablets.
4. Oral NSAIDs, at the lowest effective dose for the shortest time, weighing gastrointestinal, kidney, and cardiovascular risks.
5. Paracetamol/acetaminophen, which recent evidence suggests is barely better than placebo for osteoarthritis, contrary to decades of guidance.
6. Intra-articular corticosteroid injection for short-term relief, with the caveat that repeated injections may accelerate cartilage loss.
7. Joint replacement for advanced disease with disabling pain. Hip and knee arthroplasty are among the most cost-effective operations in medicine, with most patients getting substantial and durable relief.

What does not work as advertised: arthroscopic surgery with meniscal debridement or lavage for degenerative knee disease performs no better than sham surgery or physiotherapy in multiple randomised trials, including a landmark sham-controlled study, and continues to be performed in large numbers. Glucosamine and chondroitin have not shown benefit over placebo in the largest independent trials. Opioids provide minimal benefit and substantial harm in chronic musculoskeletal pain.

Rheumatoid and inflammatory arthritis

Covered in Chapter 47, and the distinction matters because treatment is entirely different:

The practical rule: prolonged morning stiffness with symmetric small-joint swelling needs urgent rheumatology referral, because the window in which treatment prevents permanent joint damage is measured in weeks to months.

Osteoporosis

In short: Silent bone loss that announces itself only when something breaks, and most people who fracture are never treated for the underlying disease.

What it is. Loss of bone mass and deterioration of bone microarchitecture, producing fragile bones that fracture from a fall from standing height or less (a fragility fracture). It is defined operationally by a bone density scan (DEXA) T-score of -2.5 or below, meaning 2.5 standard deviations below the mean for a healthy young adult.

What actually goes wrong. Bone is constantly remodelled: osteoclasts dissolve old bone and osteoblasts build new bone, with the whole skeleton turning over every ten years or so. Peak bone mass is reached in the late twenties, and thereafter resorption slightly exceeds formation. Anything that tips the balance further accelerates loss:

• Oestrogen deficiency at menopause is the single biggest factor. Oestrogen restrains osteoclasts, and its withdrawal produces rapid bone loss for 5 to 10 years.
• Corticosteroids, which suppress osteoblasts and increase resorption. Long-term steroid use is the commonest secondary cause.
• Immobility, since bone responds to loading. Bed rest and spaceflight both cause dramatic bone loss.
• Smoking, excess alcohol, low body weight, low calcium and vitamin D, and a range of diseases including hyperthyroidism, coeliac disease, hyperparathyroidism, chronic kidney disease, and hypogonadism.

What it does. Nothing at all until a fracture. The characteristic sites are the wrist (often the first, in the fifties and sixties), the spine (vertebral compression fractures, which cause height loss, a stooped posture, and chronic back pain, and which are frequently not diagnosed at all because two-thirds occur without a memorable event), and the hip, which is the catastrophic one.

A hip fracture is a life-changing event. Roughly 20 to 30 percent of older patients die within a year, mostly from complications of immobility and the physiological insult of surgery in a frail person. Of the survivors, a large fraction never return to their previous level of independence and many move into residential care. A first fragility fracture roughly doubles the risk of the next one, which makes it the clearest possible signal to treat, and which is why the failure to do so is so striking: audits repeatedly find that most patients who present with a fragility fracture are discharged without bone assessment or treatment.

Treatment:

Plus calcium and vitamin D sufficiency (as an adjunct, not a treatment on its own), weight-bearing and resistance exercise, and, crucially, falls prevention: strength and balance training, medication review (sedatives, antihypertensives causing postural drops), vision correction, home hazard assessment. Preventing the fall matters as much as strengthening the bone, because almost all hip fractures involve a fall.

Side effects worth knowing: bisphosphonates cause oesophageal irritation (hence the instruction to take them with a full glass of water and remain upright for 30 minutes) and, rarely, osteonecrosis of the jaw and atypical femoral fractures. Both rare complications are heavily publicised and vastly outweighed by the fractures prevented: the atypical fracture risk is on the order of 1 per 10,000 patient-years against a background of preventing thousands of ordinary fractures. Fear of these rare harms has measurably reduced treatment rates and increased hip fractures, which is a case study in how risk communication can cause net harm.

Gout

In short: Crystals forming because humans lost the enzyme that disposes of uric acid, and one of the few genuinely curable forms of arthritis, usually treated only in flares.

What it is. Deposition of monosodium urate crystals in joints and tissues, caused by persistently high blood uric acid.

What actually goes wrong. Uric acid is the end product of purine breakdown. Most mammals have an enzyme (uricase) that degrades it further; humans lost that gene during primate evolution, so we run uric acid levels close to its solubility limit. Above roughly 6.8 mg/dL (about 400 micromol/L), urate can crystallise, particularly in cooler peripheral joints, which is why the base of the big toe is the classic site. Crystals are recognised by the innate immune system through the NLRP3 inflammasome, which triggers a violent interleukin-1-driven inflammatory response.

What it does. An acute attack comes on over hours, often at night: a joint that is exquisitely painful, red, hot, and swollen, so tender that a bedsheet is unbearable. Untreated, it settles over one to two weeks. Over years, untreated gout produces tophi (visible chalky deposits in joints, ears, and tendons), joint destruction, and kidney stones.

Who gets it. Men far more than premenopausal women (oestrogen promotes urate excretion). Risk factors: genetics (variants in the kidney urate transporters SLC2A9 and ABCG2 account for a large share of variation in uric acid levels), chronic kidney disease, diuretics, obesity, alcohol (beer especially, because of its purine content), sugar-sweetened drinks and fructose, red meat and shellfish, and, historically, lead exposure. Gout is strongly associated with hypertension, diabetes, kidney disease, and cardiovascular disease.

Treatment, and this is where the failure lies. Attacks are treated with NSAIDs, colchicine (which disrupts the microtubules neutrophils need to migrate and to assemble the inflammasome), or corticosteroids.

But the disease is the crystals, not the attack. Urate-lowering therapy, principally allopurinol (which inhibits xanthine oxidase, the enzyme that makes uric acid) or febuxostat, taken continuously and titrated until blood urate is below about 6 mg/dL (360 micromol/L), dissolves existing crystals over months to years and eventually eliminates attacks entirely. This is a genuine cure in a chronic disease, achievable with a cheap generic tablet, and studies consistently find that only a minority of gout patients are on adequate urate-lowering therapy at an adequate dose with the target checked.

Two practical points that cause most of the failures: starting urate-lowering therapy can precipitate an attack as crystals dissolve, so it is started with anti-inflammatory cover for several months, and patients who are not warned about this conclude the drug caused the gout and stop it. And allopurinol should not be stopped during an attack, another common error.

Dietary change alone lowers urate only modestly, roughly 10 to 15 percent at best, which is usually not enough to reach the target. Diet advice given instead of urate-lowering therapy is a substitution of moralism for treatment.

Allopurinol hypersensitivity syndrome, a severe skin and systemic reaction, is strongly associated with HLA-B*58:01, common in Han Chinese, Thai, and Korean populations, and testing before prescribing is recommended in those groups: another routine pharmacogenomic screen.

Low back pain

In short: The world's leading cause of disability, mostly without an identifiable structural cause, and scanning it routinely makes outcomes worse.

What it is. Pain in the lumbar region, with or without radiation into the leg. It is the single largest contributor to years lived with disability worldwide, affecting around 600 million people at any time, and roughly 80 percent of people experience it at some point.

What actually goes wrong. In more than 90 percent of cases, no specific structural cause can be identified, and it is classified as non-specific low back pain. The pain is real; the search for a single damaged part usually fails.

The reason is a genuine disconnect between imaging and symptoms. Systematic reviews of spinal MRI in people with no back pain at all find disc degeneration in around 37 percent of 20-year-olds and 96 percent of 80-year-olds, disc bulges in the majority of middle-aged people, and disc protrusions in roughly a third. These findings are age-related, like grey hair, and finding one in a person with back pain does not establish that it is the cause.

The clinical consequence is important and counterintuitive: routine imaging for non-specific back pain makes outcomes worse. Randomised trials find no benefit and show that patients who are imaged report more pain, more disability, and undergo more procedures, because being told your spine is degenerated changes how you move and what you believe about your body.

What must be excluded are the specific causes, identified by "red flags": cancer (history of malignancy, unexplained weight loss, night pain), infection (fever, intravenous drug use, immunosuppression), fracture (significant trauma, osteoporosis, steroid use), cauda equina syndrome (bladder or bowel dysfunction, saddle numbness, bilateral leg weakness: a surgical emergency), and inflammatory back pain (age under 45, insidious onset, morning stiffness over 30 minutes, improvement with exercise and not with rest, waking in the second half of the night, suggesting axial spondyloarthritis, which is treatable and typically diagnosed after years of delay).

Treatment for non-specific back pain, which has changed substantially:

• Stay active. Bed rest is harmful and delays recovery. This reversed the advice of a generation ago.
• Reassurance and education, including explaining that pain does not equal damage, which is itself an evidence-based intervention.
• Exercise therapy of essentially any type, with adherence mattering more than the specific method.
• Manual therapy, massage, yoga, tai chi, and cognitive behavioural approaches for chronic pain, all with modest effect sizes.
• NSAIDs for short-term relief. Paracetamol is ineffective for acute back pain by trial evidence.
• Not opioids, which perform no better than NSAIDs for back pain and carry the harms of Chapter 43.
• Surgery for specific indications: cauda equina, progressive neurological deficit, or persistent radicular pain from a confirmed compressive lesion. Fusion surgery for non-specific back pain has weak evidence and high rates of persistent pain.

What the person can do

In short: Movement is treatment and rest is harm, for every condition in this chapter.

• Move. For every condition in this chapter, movement is treatment and rest is harm. Osteoarthritic joints, osteoporotic bones, and painful backs all do better with load than without.
• Build strength before you need it. Peak bone mass is set by the late twenties and muscle mass declines from midlife. Resistance training in middle age protects both.
• Get a bone assessment after any fracture from a low-impact fall after 50. If it is not offered, ask for it.
• Prevent falls actively: balance and strength training (tai chi has good evidence), medication review, vision checks, and removing home hazards.
• For gout, ask for a urate target, not just attack treatment. Ask what your urate level is, what the target is, and whether the allopurinol dose has been titrated to reach it.
• Do not chase a scan for ordinary back pain. Ask instead whether there are red flags, and if not, focus on activity and time.
• Manage weight where it applies, which reduces both knee osteoarthritis symptoms and gout.
• Take vitamin D and calcium sufficiency seriously in older age, alongside, not instead of, proper osteoporosis treatment.

Living with it

Musculoskeletal disease is the largest cause of disability and among the least prioritised, because it rarely kills and because pain is invisible. The consequences are chronic: lost work, lost independence, social withdrawal, and the depression that accompanies persistent pain and reinforces it.

Two systemic failures dominate. The treatment gap in osteoporosis, where an effective, cheap, proven therapy is not given to most of the people who have already fractured. And the management of chronic back pain, where decades of imaging, injections, opioids, and surgery have produced enormous cost and, at population level, no improvement in outcomes. Fracture liaison services (which automatically assess anyone presenting with a fragility fracture) and back pain pathways emphasising activity and self-management are the corrections, and both are underimplemented.

What's next

• Disease-modifying osteoarthritis drugs, which do not yet exist. Candidates targeting cartilage breakdown, bone remodelling, and pain pathways are in trials, and nerve growth factor inhibitors showed strong analgesia with a signal of accelerated joint destruction.
• Better fracture risk prediction and automated case-finding from routine imaging, since vertebral fractures are visible on scans done for other reasons and are systematically not reported.
• Sarcopenia as a treatable condition, since muscle loss underlies falls, fractures, and frailty, and is currently addressed almost entirely by exercise.
• Precision approaches in back pain, identifying the subgroups within "non-specific" that respond to specific treatments, which is where the field's best hope of progress lies.

Sources and notes

Low back pain burden: Global Burden of Disease studies, consistently ranking it first for years lived with disability, with GBD 2021 estimating around 600 million people affected. Imaging findings in asymptomatic people: Brinjikji et al., American Journal of Neuroradiology, 2015. Harms of routine imaging: Chou et al., The Lancet, 2009, and subsequent guideline reviews. Arthroscopic knee surgery: Moseley et al., NEJM, 2002 (sham-controlled), and Sihvonen et al., NEJM, 2013 (meniscectomy versus sham). Exercise for osteoarthritis: Cochrane reviews. Hip fracture one-year mortality: multiple national registry analyses, typically 20 to 30 percent in older patients. Osteoporosis treatment gap: national audits including the UK Fracture Liaison Service database and US claims analyses. Atypical femoral fracture risk: Black et al., NEJM, 2020. Denosumab discontinuation rebound: Cummings et al., Journal of Bone and Mineral Research, 2018. Gout treat-to-target evidence and adherence: ACR and EULAR guidelines and health system audits. HLA-B*58:01 and allopurinol: Hung et al., PNAS, 2005. Uricase gene loss in primates: standard evolutionary biology literature.

Open questions. No treatment yet modifies the course of osteoarthritis. Why the same imaging findings cause pain in one person and not another is unresolved, and is the central question in musculoskeletal medicine.

Next: the chemical messengers that set the pace of everything else. 👉